CANNABIDIOL

SCIENTIFIC RESEARCH PUBLICATIONS

The molecular mechanisms that underpin the biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation
Maayah ZH, Takahara S, Ferdaoussi M and Dyck JRB
Cannabis has been shown to be beneficial in the treatment of pain and inflammatory diseases. The biological effect of cannabis is mainly attributed to two major cannabinoids, tetrahydrocannabinol and cannabidiol. In the majority of studies to-date, a purified tetrahydrocannabinol and cannabidiol alone or in combination have been extensively examined in many studies for the treatment of numerous disorders including pain and inflammation. However, few studies have investigated the biological benefits of full-spectrum cannabis plant extract. Given that cannabis is known to generate a large number of cannabinoids along with numerous other biologically relevant products including terpenes, studies involving purified tetrahydrocannabinol and/or cannabidiol do not consider the potential biological benefits of the full-spectrum cannabis extracts. This may be especially true in the case of cannabis as a potential treatment of pain and inflammation. Herein, we review the pre-clinical physiological and molecular mechanisms in biological systems that are affected by cannabis.
Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol
Madden K, Tanco K and Bruera E
The use of cannabidiol products in pediatric patients is becoming more frequent because of the increased ease of accessibility. This case report illustrates the potential for cannabidiol to interact with stable medication regimens. A 13-year-old girl with metastatic cancer and chronic pain presented with increased sleepiness and fatigue. She had been started on 7.5 mg of methadone by mouth twice daily 4 months earlier. Unbeknownst to her physicians, her parents had commenced her on cannabidiol and subsequently increased the dose leading up to her presentation, thinking it would result in tumor shrinkage. The initial serum methadone level was 271 ng/mL, which decreased to 125 ng/mL 14 days after discontinuing cannabidiol. The reduced serum methadone level coincided with improved sleepiness and fatigue. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol.
Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty
Runner RP, Luu AN, Nassif NA, Scudday TS, Patel JJ, Barnett SL and Gorab RS
Given the opioid crisis in America, patients are trying alternative medications including tetrahydrocannabinol (THC) and other cannabidiol (CBD) containing products in the perioperative period, especially in states where these products are legal. This study sought to analyze usage rates of CBD/THC products in the perioperative period for primary unilateral total hip and knee arthroplasty (THA/TKA) patients and identify a possible association with post-operative opioid use.
Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature
Inglet S, Winter B, Yost SE, Entringer S, Lian A, Biksacky M, Pitt RD and Mortensen W
To compile and synthesize the available literature describing medical cannabis use across various disease states. PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.
An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain
Zhu YF, Linher-Melville K, Niazmand MJ, Sharma M, Shahid A, Zhu KL, Parzei N, Sidhu J, Haj C, Mechoulam R and Singh G
Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable.
Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain
Abraham AD, Leung EJY, Wong BA, Rivera ZMG, Kruse LC, Clark JJ and Land BB
Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆-tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine. This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.
The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis
Maayah ZH, Takahara S, Ferdaoussi M and Dyck JRB
Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain. The benefits of cannabis are mediated largely by cannabinoids, the most prominent of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). As such, THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation. While a plethora of studies have examined the biochemical effects of purified THC and/or CBD, only a few have focused on the effects of full-spectrum cannabis plant extract. Accordingly, studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts. Indeed, the cannabis plant produces a wide range of cannabinoids, terpenes, flavonoids, and other bioactive molecules which are likely to contribute to the different biological effects. The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis.
Raman-Based Differentiation of Hemp, Cannabidiol-Rich Hemp, and Cannabis
Sanchez L, Baltensperger D and Kurouski D
Hemp () has been used to treat pain as far back as 2900 B.C. Its pharmacological effects originate from a large variety of cannabinols. Although more than 100 different cannabinoids have been isolated from plants, clear physiological effects of only a few of them have been determined, including delta-9 tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG). While THC is an illicit drug, CBD and CBG are legal substances that have a variety of unique pharmacological properties such as the reduction of chronic pain, inflammation, anxiety, and depression. Over the past decade, substantial efforts have been made to develop Cannabis varieties that would produce large amounts of CBD and CBG. Ideally, such plant varieties should produce very little (below 0.3%) if any THC to make their cultivation legal. The amount of cannabinoids in the plant material can be determined using high performance liquid chromatography (HPLC). This analysis, however, is nonportable, destructive, and time and labor consuming. Our group recently proposed to use Raman spectroscopy (RS) for confirmatory, noninvasive, and nondestructive differentiation between hemp and cannabis. The question to ask is whether RS can be used to detect CBD and CBG in hemp, as well as enable confirmatory differentiation between hemp, cannabis, and CBD-rich hemp. In this manuscript, we show that RS can be used to differentiate between cannabis, CBD-rich plants, and regular hemp. We also report spectroscopic signatures of CBG, cannabigerolic acid (CBGA), THC, delta-9-tetrahydrocannabinolic acid (THCA), CBD, and cannabidiolic acid (CBDA) that can be used for Raman-based quantitative diagnostics of these cannabinoids in plant material.
Antinociceptive and Immune Effects of Delta-9-Tetrahydrocannabinol or Cannabidiol in Male Versus Female Rats with Persistent Inflammatory Pain
Britch SC, Goodman AG, Wiley JL, Pondelick AM and Craft RM
Chronic pain is the most common reason reported for using medical cannabis. The goal of this research was to determine whether the two primary phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective treatments for persistent inflammatory pain. In experiment 1, inflammation was induced by intraplantar injection of Complete Freund's adjuvant (CFA). Then THC (0.0-4.0 mg/kg, i.p.) or CBD (0.0-10 mg/kg, i.p.) was administered twice daily for 3 days. On day 4, THC, CBD, or vehicle was administered, and allodynia, hyperalgesia, weight-bearing, locomotor activity, and hindpaw edema were assessed 0.5-4 hours postinjection. In experiment 2, CFA or mineral oil (no-pain control)-treated rats were given THC (2.0 mg/kg, i.p.), CBD (10 mg/kg, i.p.), or vehicle in the same manner as in experiment 1. Four hours postinjection on day 4, serum samples were taken for analysis of cytokines known to influence inflammatory pain: interleukin (IL)-1, IL-6, IL-10, interferon (IFN)-, and tumor necrosis factor (TNF)- THC dose-dependently reduced pain-related behaviors but did not reduce hindpaw edema, and little tolerance developed to THC's effects. In contrast, CBD effects on inflammatory pain were minimal. THC produced little to no change in serum cytokines, whereas CBD decreased IL-1, IL-10, and IFN- and increased IL-6. Few sex differences in antinociception or immune modulation were observed with either drug, but CFA-induced immune activation was significantly greater in males than females. These results suggest that THC may be more beneficial than CBD for reducing inflammatory pain in that THC maintains its efficacy with short-term treatment in both sexes and does not induce immune activation. SIGNIFICANCE STATEMENT: The pain-relieving effects of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are examined in male and female rats with persistent inflammatory pain to determine whether individual phytocannabinoids could be a viable treatment for men and women with chronic inflammatory pain. Additionally, sex differences in the immune response to an adjuvant and to THC and CBD are characterized to provide preliminary insight into immune-related effects of cannabinoid-based therapy for pain.
Does the addition of cannabidiol alongside current drug treatments reduce pain in dogs with osteoarthritis?
Morrow L and Belshaw Z
Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats
Izgelov D, Freidman M and Hoffman A
The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.
Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice
Assareh N, Gururajan A, Zhou C, Luo JL, Kevin RC and Arnold JC
The major phytocannabinoid cannabidiol (CBD) has anxiolytic properties and lacks tetrahydrocannabinol-like psychoactivity. Cannabidiolic acid (CBDA) is the acidic precursor to CBD, and this compound appears more potent than CBD in animal models of emesis, pain and epilepsy. In this short report, we aimed to examine whether CBDA is more potent than CBD in disrupting expression of conditioned fear and generalised anxiety-related behaviour induced by Pavlovian fear conditioning. Mice underwent fear conditioning and 24 h later were administered CBD and CBDA before testing for fear expression and generalized anxiety-like behaviour. We found that CBD and CBDA had dissociable effects; while CBD but not CBDA disrupted cued fear memory expression, CBDA but not CBD normalized trauma-induced generalized anxiety-related behaviour. Neither phytocannabinoid affected contextual fear expression. Our findings form the basis for future experiments examining whether phytocannabinoids, alone and in combination, are effective in these mouse models of fear and anxiety.
[CHARACTERISTICS OF MEDICAL CANNABIS USAGE AMONG PATIENTS WITH FIBROMYALGIA]
Habib G and Levinger U
Medical cannabis (MC) is becoming more and more popular among patients with chronic pain syndromes. In this study we evaluated the characteristics of MC use among patients with fibromyalgia.
Editorial: Brain Mediators of the Cannabis-Prodromal Psychosis Connection
Lange N
The article by Yu and Jia et al. in this issue of the Journal investigates the role of a subregion of the parahippocampal gyrus called the right uncus ("hook") as a possible mediator of the known increase of psychotic-like experiences (PLEs) due to the consumption of cannabinoids (ie, cannabis). The authors chose a pattern of plausible inference worthy of pursuit. Cannabis continues to be one of the most widely used drugs globally, only behind alcohol, caffeine, and tobacco; 188 million people used cannabis worldwide in 2017. In January 2019, the WHO's Expert Committee on Drug Dependence (ECDD) recommended that cannabis be no longer classified as a Schedule IV drug (its medical potential is now deemed to outweigh its abuse potential). It should be noted that cannabidiol (CBD) is a non-psychoactive component of cannabis that has medicial uses in reducing pain and inflammation, controlling epileptic seizures, and possibly even treating mental illness and addiction. As more world governments legalize cannabis for recreational use, and owing to the widening availability of higher tetrahydrocannabinol content variants of cannabis, the number of cannabis users is increasing rapidly, which in turn increases the number of people having PLEs worldwide. Schizophrenia is one of the top 15 leading causes of disability worldwide. The estimated prevalence of schizophrenia and related psychotic disorders in the United States in 2005 ranged from 0.25% to 0.64%; a meta-analysis a decade later found the lifetime prevalence worldwide to be 0.48% with interquartile range 0.34% to 0.85%. The high variability of sampling domains, diagnostic criteria, data availability and analytic methods employed preclude reliable estimates of incidence and prevalence increases of schizophrenia at present.
The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model
Vigil JM, Montera MA, Pentkowski NS, Diviant JP, Orozco J, Ortiz AL, Rael LJ and Westlund KN
Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring '' pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of "full-spectrum" whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice.
Nabiximols plus robotic assisted gait training in improving motor performances in people with Multiple Sclerosis
Calabrò RS, Russo M, Naro A, Ciurleo R, D'Aleo G, Rifici C, Balletta T, La Via C, Destro M, Bramanti P and Sessa E
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain.
Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer
Afrin F, Chi M, Eamens AL, Duchatel RJ, Douglas AM, Schneider J, Gedye C, Woldu AS and Dun MD
Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆-tetrahydrocannabinol (∆-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.
Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs
Jacobson KA and Reitman ML
Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g., ticagrelor, ethanol, and cannabidiol), affecting intracellular metabolic pathways (e.g., methotrexate, nicotinamide riboside, salicylate, and 5-aminoimidazole-4-carboxamide riboside), or undetermined means (e.g., acupuncture). However, other compounds bind ARs in addition to their canonical 'on-target' activity (e.g., mefloquine). The strength of experimental support for an adenosine-related role in a drug's effects varies widely. AR knockout mice are the 'gold standard' method for investigating an AR role, but few drugs have been tested on these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.
Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?
Martínez V, Iriondo De-Hond A, Borrelli F, Capasso R, Del Castillo MD and Abalo R
is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes. Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol. The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions. Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions. Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract. With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.
Cannabis-based medicinal products: summary of NICE guidance
Chang-Douglass S, Mulvihill C, Pilling S and
Characteristics of Older Adults Who Were Early Adopters of Medical Cannabis in the Florida Medical Marijuana Use Registry
Brown JD, Costales B, van Boemmel-Wegmann S, Goodin AJ, Segal R and Winterstein AG
Use of medical marijuana is increasing in the United States and older adults are the fastest growing user group. There is little information about the characteristics and outcomes related to medical marijuana use. This study is a descriptive analysis of older adults (aged ≥50 years old) who were early adopters of a medical marijuana program in the U.S. state of Florida. Per state legislation, initial and follow-up treatment plans were submitted to the University of Florida College of Pharmacy. Data collection included demographics, clinical history, medical conditions, substance use history, prescription history, and health status. Follow-up treatment plans noted changes in the chief complaint and actions taken since the initial visit. Of the state's 7548 registered users between August 2016 and July 2017, = 4447 (58.9%) were older adults. Patients utilized cannabidiol (CBD)-only preparations (45%), preparations that had both tetrahydrocannabinol (THC) and CBD (33.3%) or were recorded to use both CBD-only and THC + CBD products (21.7%). The chief complaints indicating medical cannabis treatment were musculoskeletal disorders and spasms (48.4%) and chronic pain (45.4%). Among other prescription medications, patients utilized antidepressants (23.8%), anxiolytics and benzodiazepines (23.5%), opioids (28.6%), and cardiovascular agents (27.9%). Among all drug classes with potential sedating effects, 44.8% of the cohort were exposed to at least one. Patients with follow-up visits (27.5%) exhibited marked improvement as assessed by the authorizing physicians. However, the patient registry lacked detailed records and linkable information to other data resources to achieve complete follow up in order to assess safety or efficacy. Future improvements to registries are needed to more adequately capture patient information to fill knowledge gaps related to the safety and effectiveness of medical marijuana, particularly in the older adult population.
A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain
Verrico CD, Wesson S, Konduri V, Hofferek CJ, Vazquez-Perez J, Blair E, Dunner K, Salimpour P, Decker WK and Halpert MM
Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. Subsequently, the therapeutic potential of both naked and liposomally encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of OA. In vitro and in mouse models, CBD significantly attenuated the production of proinflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of OA. Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.
Cannabis sativa: Much more beyond Δ-tetrahydrocannabinol
Alves P, Amaral C, Teixeira N and Correia-da-Silva G
Cannabis is the most used illicit drug worldwide and its medicinal use is under discussion, being regulated in several countries. However, the psychotropic effects of Δ-tetrahydrocannabinol (THC), the main psychoactive compound of Cannabis sativa, are of concern. Thus, the interest in the isolated constituents without psychotropic activity, such as cannabidiol (CBD) and cannabidivarin (CBDV) is growing. CBD and CBDV are lipophilic molecules with poor oral bioavailability and are mainly metabolized by cytochrome P450 (CYP450) enzymes. The pharmacodynamics of CBD is the best explored, being able to interact with diverse molecular targets, like cannabinoid receptors, G protein-coupled receptor-55, transient receptor potential vanilloid 1 channel and peroxisome proliferator-activated receptor-γ. Considering the therapeutic potential, several clinical trials are underway to study the efficacy of CBD and CBDV in different pathologies, such as neurodegenerative diseases, epilepsy, autism spectrum disorders and pain conditions. The anti-cancer properties of CBD have also been demonstrated by several pre-clinical studies in different types of tumour cells. Although less studied, CBDV, a structural analogue of CBD, is receiving attention in the last years. CBDV exhibits anticonvulsant properties and, currently, clinical trials are underway for the treatment of autism spectrum disorders. Despite the benefits of these phytocannabinoids, it is important to highlight their potential interference with relevant physiologic mechanisms. In fact, CBD interactions with CYP450 enzymes and with drug efflux transporters may have serious consequences when co-administered with other drugs. This review summarizes the therapeutic advances of CBD and CBDV and explores some aspects of their pharmacokinetics, pharmacodynamics and possible interactions. Moreover, it also highlights the therapeutic potential of CBD and CBDV in several medical conditions and clinical applications.
Novel approaches and current challenges with targeting the endocannabinoid system
Morales P and Jagerovic N
: The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome. Ligands targeting the canonical cannabinoid receptors, CB and CB, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others.: Challenges in the pharmacology of cannabinoids arise from its pharmacokinetics, off-target effects, and psychoactive effects. In this context, the current review outlines the novel molecular approaches emerging in the field discussing their clinical potential.: Even if orthosteric CB and CB ligands are on the forefront in cannabinoid clinical research, emerging strategies such as allosteric or biased modulation of these receptors along with controlled off-targets effects may increase the therapeutic potential of cannabinoids.
[Cannabidiol in cancer treatment]
Likar R, Köstenberger M and Nahler G
Cannabis was used for cancer patients as early as about 2500 years ago. Experimental studies demonstrated tumor-inhibiting activities of various cannabinoids more than 40 years ago. In view of the status of tetrahydrocannabinol (THC) as a regulated substance, non-psychotomimetic cannabidiol (CBD) is of particular importance.
A Case of Toxicity from Cannabidiol Gummy Ingestion
Bass J and Linz DR
A 56-year-old male with no known history of substance abuse and no known prior medical conditions presented via ambulance to the emergency department after being found by coworkers with bizarre behavior, vomiting, and slurred speech. He had legally purchased cannabidiol (CBD) gummies marketed for pain and anxiety relief at a gas station several hours prior. Vitals upon arrival were temperature 36.8 Celsius, heart rate (HR) 79, respiratory rate (RR) 12, blood pressure (BP) 113/60, and oxygen saturation (O) of 84% on room air that improved upon arousal. Physical exam showed an obese man in no acute distress with a depressed level of consciousness but who awoke to painful stimuli. Neuro exam was significant for dysarthric, hypophonic speech. Labs were significant for a primary respiratory acidosis with concomitant mild lactic acid elevation, normal bicarbonate, and normal anion gap. A comprehensive urine toxicology screen including cannabis was negative. Vital signs three hours after presentation deteriorated, showing: HR 47, RR 8-12, BP 88/52, O 78%. Electrocardiogram (EKG) revealed sinus bradycardia. The patient progressively became more obtunded and required constant stimuli in order to maintain a patent airway. Non-invasive positive pressure ventilation was not administered due to persistent emesis. The patient underwent supportive care with intravenous fluids, oxygen, anti-emetics, continuous stimulation, and close neurologic monitoring with full recovery by the following morning. Further, patient history revealed that he had consumed two packages of CBD gummies, totaling 370 mg total of CBD (serving size on the package was 30 mg). He felt the products were healthy and safe based on packaging and therefore did not believe they would have any adverse effects. CBD is one of many cannabinoids found in marijuana and marijuana-derived products. It is generally considered safe unlike its more psychoactive counterpart, tetrahydrocannabinol (THC), which has been linked to seizures, respiratory depression, and cardiovascular complications. CBD has surged in popularity recently, being marketed in oils, capsules, and candies as a health supplement, claiming to treat a wide variety of medical conditions such as glaucoma, pain, and even having beneficial effects on cancer prevention. Most currently available studies do not look at isolated CBD nor their synthetic equivalents, and purity is not guaranteed, thus leading to unforeseen side effects and toxicities. Moreover, these compounds do not show on traditional toxicology screens, posing a diagnostic dilemma for physicians. This case of respiratory depression and cardiovascular compromise in a relatively healthy man is just one example of the importance of considering synthetic CBD toxicity in the differential diagnosis, as there is little data available for recognizing and treating this condition.
A cautious hope for cannabidiol (CBD) in rheumatology care
Fitzcharles MA, Clauw DJ and Hauser W
Cannabidiol (CBD), a major metabolite of Cannabis sativa, is popularized as a medicinal product, with potential for analgesic, anti-inflammatory and antioxidant effects. CBD may hold promise as a treatment in rheumatic diseases, but evidence to date remains preclinical. Preclinical effects on pain and inflammation is encouraging, but clinical study is lacking with only a single study in knee osteoarthritis reporting promising effect on symptoms. CBD products are freely available over the counter and marketed as food supplements or wellness products. The World Health Organization has identified pure CBD as safe and without abuse potential, but products are not subject to drug regulatory standards leading to inconsistency in manufacturing practices and quality of products. Not only have molecular concentrations of CBD been identified as inaccurate, but there are concerns for contaminants including heavy metals, pesticides, microbes and mycotoxins, as well as added THC. Drug-drug interactions pose a potential risk due to metabolism via the CYP P450 enzyme pathway. Patients wishing to use CBD should obtain a product with certification of Good Manufacturing Practices, initiate treatment with a nighttime low dose and have defined outcome goals within a reasonable time frame. Treatments should not be managed by non-medical dispensary personnel. The hope that CBD may be a useful therapy must be substantiated by sound scientific study.
Cannabis Use in Children With Pantothenate Kinase-Associated Neurodegeneration
Wilson JL, Gregory A, Wakeman K, Freed A, Rai P, Roberts C, Hayflick SJ and Hogarth P
Pantothenate kinase-associated neurodegeneration is characterized by severe, progressive dystonia. This study aims to describe the reported usage of cannabis products among children with pantothenate kinase-associated neurodegeneration.
NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration
Heimann AS, Giardini AC, Sant'Anna MB, Dos Santos NB, Gewehr MCF, Munhoz CD, Castro LM, Picolo G, Remer RA and Ferro ES
Previous studies suggested the pharmacological potential of rat hemopressin (PVNFKFLSH) and its shorter synthetic peptide NFKF, to protect from pilocarpine-induced seizures in mice. Orally administered NFKF was shown to be hundred times more potent than cannabidiol in delaying the first seizure induced by pilocarpine in mice. Here, using an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis we have shown that C57BL/6 J mice orally administrated with NFKF (500 μg/kg) presented better EAE clinical scores and improved locomotor activity compared to saline administrated control mice. NFKF blocked the production of IL-1beta and IL-6, and has high scores binding cannabinoid type 2 receptors. Therefore, NFKF is an exciting new possibility to neurodegenerative diseases therapeutics.
Nutrition and immunology in mental health: Precision medicine and integrative approaches to address unmet clinical needs in psychiatric treatments
Chang JP and Su KP
The 'monoamine hypothesis' is insufficient in approaching the aetiology of psychiatric disorders or in developing novel therapies. Accumulating evidence suggests that inflammatory regulation plays an important role in pathophysiology and therapeutic mechanism across the major psychiatric disorders. "Inflammation theory" might not be the full answer for the big picture of mental disorders, but it might explain high occurrence of somatic symptoms and comorbidity of physical illness in certain subtypes of the heterogeneous groups. Due to the complexity of clinical manifestations and bio-psycho-social etiology, each single treatment shows only small effectiveness with limited effect sizes when compared with placebo. Unfortunately, clinicians are still struggling with trial-and-error practice without any reliable clinical or biological markers to predict therapeutic responses. Therefore, it is important to open up our minds to integrative approaches such dietary modification and nutraceutical prescription. In this special issue, we included 15 papers discussing the role of nutrition (blueberries, omega-3 polyunsaturated fatty acids, melatonergic agonist, S-Adenosyl-L-Methionine, Cannabidiol and Kratom) in the context of immunoregulation across different psychiatric disorders from depression, bipolar disorders, and schizophrenia to alcohol-induced dementia and anorexia nervosa. Moreover, we also included research in perinatal depression that highlight the role of estradiol and the component of breast milk and the association with the neurodevelopment of the offspring. In addition, several articles focused on the role of microbiota in mental health and pain as recent research has pointed to the gut-brain axis as a main regulator of brain, behaviour and immunity. Lastly, inflammatory mechanisms underlying psychiatric disorders including alcohol induced dementia and anorexia nervosa are also highlighted in the special issue.
Cannabinoids, Blood-Brain Barrier, and Brain Disposition
Calapai F, Cardia L, Sorbara EE, Navarra M, Gangemi S, Calapai G and Mannucci C
Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds. THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain. The present article is an overview about THC and CBD crossing the blood-brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS. Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.
Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial
Meuth SG, Henze T, Essner U, Trompke C and Vila Silván C
To determine whether differences in disability status, spasticity severity, and spasticity duration at treatment start in patients with resistant multiple sclerosis (MS) spasticity might influence response to add-on tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (nabiximols) versus further re-adjustment of optimized first-line antispasticity medication. Using the database from the Sativex as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) study, this post hoc analysis evaluated spasticity severity (0-10 numerical rating scale [NRS] scores) and pain severity (0-10 NRS scores) evolution from randomization (baseline) to week 12 (end of double-blind treatment) in defined subgroups: Expanded disability status scale [EDSS] score subgroups (<6 and ≥6); spasticity severity 0-10 NRS score subgroups (4 to ≤6 and >6), and spasticity duration subgroups (<5 and ≥5 years). THC:CBD oromucosal spray (nabiximols) halved mean severity scores for spasticity and pain in all subgroups. Active treatment significantly improved mean spasticity severity scores versus placebo from week 4 onwards in both EDSS subgroups, in the severe spasticity subgroup, and in both spasticity duration subgroups. Active treatment significantly improved mean pain severity scores versus placebo in the ≥6 EDSS subgroup, in the severe spasticity subgroup and in both spasticity duration subgroups. Add-on THC:CBD oromucosal spray (nabiximols) consistently relieves resistant spasticity across subgroups defined by baseline EDSS score, spasticity severity NRS score and spasticity duration. Patients with moderate resistant MS spasticity benefit numerically from treatment; patients with severe resistant spasticity achieve significant therapeutic gains. Spasticity-associated pain often improves similarly in the same subgroups.
Social media surveillance for perceived therapeutic effects of cannabidiol (CBD) products
Tran T and Kavuluru R
CBD products have risen in popularity given CBD's therapeutic potential and lack of legal oversight, despite lacking conclusive scientific evidence for widespread over-the-counter usage for many of its perceived benefits. While medical evidence is being generated, social media surveillance offers a fast and inexpensive alternative to traditional surveys in ascertaining perceived therapeutic purposes and modes of consumption for CBD products.
The nephrologist's guide to cannabis and cannabinoids
Rein JL
Cannabis (marijuana, weed, pot, ganja, Mary Jane) is the most commonly used federally illicit drug in the United States. The present review provides an overview of cannabis and cannabinoids with relevance to the practice of nephrology so that clinicians can best take care of patients.
Cannabidiol: A Brief Review of Its Therapeutic and Pharmacologic Efficacy in the Management of Joint Disease
Gusho CA and Court T
Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use. Cannabidiol (CBD), a commercially available, non-neurotropic marijuana constituent, has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses. Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures. However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts and retrospective reviews, perhaps due to legal ramifications limiting the enrollment of patients. The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty. Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD use in perioperative pain management. Additionally, a number of CBD products currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.
Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease
Crivelaro do Nascimento G, Ferrari DP, Guimaraes FS, Del Bel EA, Bortolanza M and Ferreira-Junior NC
Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.
Cannabinoids in the Treatment of Back Pain
Kim TE, Townsend RK, Branch CL, Romero-Sandoval EA and Hsu W
Marijuana is increasingly utilized for the treatment of multiple medical problems, including back pain, in the United States. Although there is strong preclinical evidence supporting the promise of cannabinoids in the treatment of back pain, there is a paucity of clinical data supporting their use in clinical practice. Opioids are an important medication for the treatment of acute and chronic back pain, but utilization of opioid-based regimens have likely contributed to the growing opioid epidemic. The significant risk of morbidity, mortality, and dependence secondary to opioid medications have increased the interest in nonopioid medications, including cannabinoid-based pain regimens, in treating back pain. This review will provide an overview on the pharmacology, drug delivery methods, clinical evidence, and safety considerations critical to understanding the potential role of cannabinoids in the treatment of back pain.
A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients
Montagnese F, Stahl K, Wenninger S and Schoser B
The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms' relief through consumption of cannabis.
CBD for Pain: Is Cannabidiol a Natural Alternative to Opioid Drugs?
Meletis C
No Abstract Available.
Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders
Fernández-Trapero M, Pérez-Díaz C, Espejo-Porras F, de Lago E and Fernández-Ruiz J
The phytocannabinoid-based medicine Sativex is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ-tetrahydrocannabinol (Δ-THC) and its metabolite 11-hydroxy-Δ-THC. Maximal plasma concentrations of both Δ-THC (C = 18.5 ng/mL) and CBD (C = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ-THC: C = 24.5 ng/mL; CBD: C = 15.2 ng/mL). 11hydroxy-Δ-THC, which is mainly formed in the liver from Δ-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1-2 h and suggested progressive accumulation after the multiple dose treatment.
Use of cannabinoid-based medicine among older residential care recipients diagnosed with dementia: study protocol for a double-blind randomised crossover trial
Timler A, Bulsara C, Bulsara M, Vickery A, Smith J and Codde J
Dementia is a neurological condition that affects the cognitive and functional ability of the brain and is the leading cause of disability among those aged 65 years and above. More effective ways to manage dementia symptoms are needed because current treatment options (antidepressants and antipsychotics) can be ineffective and are associated with substantial side effects, including increased rate of mortality. Cannabinoid-based medicine (CBM) has shown an ability to inhibit some symptoms associated with dementia, and the adverse effects are often minimal; yet, little research has explored the use of CBM among this population.
Efficacy and safety of a supplement combination for hand osteoarthritis pain: protocol for an internet-based randomised placebo-controlled trial (The RADIANT study)
Liu X, Robbins S, Eyles J, Fedorova T, Virk S, Deveza LA, McLachlan A and Hunter D
Hand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic relief. A combination of two or more supplements is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to investigate the efficacy of a supplement combination for treating symptomatic HOA in comparison to placebo.
Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives
Klein M, Gonçalves Salum F, Cherubini K and Zancanaro de Figueiredo MA
The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.
Cannabis Use and Cognition in Adults Prescribed Opioids for Persistent Pain
Wildes M, Bigand TL, Layton ME and Wilson M
Adults with persistent pain frequently report cannabis use to help manage their symptoms. The impact of cannabis use on cognition in the presence of concurrent symptoms of depression and anxiety is poorly understood.
Tetrahydrocannabinol and Cannabidiol Use in an Outpatient Palliative Medicine Population
Highet BH, Lesser ER, Johnson PW and Kaur JS
Palliative medicine physicians are challenged by lack of guidance regarding effectiveness and dosing of cannabis products in the setting of their emerging popularity.
The Void in Clinician Counseling of Cannabis Use
Calcaterra SL, Cunningham CO and Hopfer CJ
As more states legalize cannabis for medical use, people increasingly use cannabis to treat medical conditions. Well-documented harms of cannabis use include increased risk of fatal auto accidents, neurocognitive deficits, and increased risk of addiction. Observational data supports the use of cannabis for pain, nausea and vomiting related to chemotherapy, and multiple sclerosis spasticity symptoms. Given potential harms versus benefits of cannabis use, how should physicians counsel patients regarding their cannabis use? This paper briefly reviews the evidence supporting medical cannabis use for pain. We consider cannabis use as a harm reduction strategy for pain management. We encourage routine, longitudinal assessments of cannabis use among patients. We discuss the commercialization of cannabis for financial gain, contributing to potent and addictive cannabis. We highlight the concerning phenomena of cannabis dispensary workers as proxy clinicians. Finally, we present three strategies to reduce public harms associated with potent cannabis use including required testing and reporting of tetrahydrocannabinol/cannabidiol concentrations, rigorous study of high-potency cannabis available for purchase in dispensaries across the USA, and large-scale efforts to measure cannabis consumption in medical records so prospective, longitudinal studies can be conducted to correlate consumption measures with medical and psychiatric outcomes.
The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence
Boyaji S, Merkow J, Elman RNM, Kaye AD, Yong RJ and Urman RD
Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain. Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits. While historically more attention has been paid to the psychoactive component of the cannabis plant Δ-tetrahydrocannabinol (THC), there have been fewer scientific studies on the medical use of the cannabidiol (CBD) - a non-psychoactive component of the cannabis plant.
Source of cannabinoids: what is available, what is used, and where does it come from?
Specchio N, Pietrafusa N and Cross HJ
Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases. Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified. Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS. The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.
Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review
Sarris J, Sinclair J, Karamacoska D, Davidson M and Firth J
Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known.
Medical cannabis and insomnia in older adults with chronic pain: a cross-sectional study
Sznitman SR, Vulfsons S, Meiri D and Weinstein G
Medical cannabis (MC) is increasingly being used for treatment of chronic pain symptoms. Among patients there is also a growing preference for the use of MC to manage sleep problems. The aim of the current study was to examine the associations between use of whole plant cannabis and sleep problems among chronic pain patients.
Hyperkinetic reaction to dihydrocodeine
van Oppen JD, Patel N and Tarique A
A young man was using dihydrocodeine analgesia for ear pain having had suppurative otitis media. He attended the emergency department with restlessness and twitching movements in his arms and legs. He had fever with otherwise normal vital signs. He had no signs of cerebellar pathology. Investigations were normal. The working diagnosis was of hyperkinetic reaction to dihydrocodeine. Symptoms resolved within 48 hours of withdrawing the drug. Serotonin toxicity is a rare side effect of dihydrocodeine. There is a theoretical basis for increased side effects when taken with cannabidiol-based substances.
Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases
Kienzl M, Storr M and Schicho R
In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant's ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.
Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study
Capano A, Weaver R and Burkman E
: Chronic pain is highly prevalent in most of the industrialized nations around the world. Despite the documented adverse effects, opioids are widely used for pain management. Cannabinoids, and specifically Cannabidiol, is proposed as an opioid alternative, having comparable efficacy with better safety profile.: We aim to investigate the impact of full hemp extract cannabidiol (CBD) on opioid use and quality of life indicators among chronic pain patients.: An initial sample of 131 patients was recruited from a private pain management center's investigative population. Ninety-seven patients completed the 8-week study. The primary inclusion criteria included patients between 30 and 65 years old with chronic pain who have been on opioids for at least 1 year. Data were collected at three different time points: baseline, 4, and 8 weeks. Opioid and other medication use were evaluated via the medication and psychiatric treatment receipt. Improvement was evaluated using four indices: Pain Disability Index (PDI-4); Pittsburgh Sleep Quality Index (PSQI), Pain Intensity and Interference (PEG); and Patient Health Questionnaire (PHQ-4).: Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements. The results indicated a significant relationship between CBD and PSQI (p = 0.003), and PEG (p = 0.006). There was a trend toward improvement but no significant relationship between CBD use and PHQ and PDI.: CBD could significantly reduce opioid use and improve chronic pain and sleep quality among patients who are currently using opioids for pain management.: This is a prospective, single-arm cohort study for the potential role of cannabinoids as an alternative for opioids. The results indicate that using the CBD-rich extract enabled our patients to reduce or eliminate opioids with significant improvement in their quality of life indices.
Cannabidiol (CBD) Consumption and Perceived Impact on Extrahepatic Symptoms in Patients with Autoimmune Hepatitis
Mathur K, Vuppalanchi V, Gelow K, Vuppalanchi R and Lammert C
Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile.
Cannabinoids and the expanded endocannabinoid system in neurological disorders
Cristino L, Bisogno T and Di Marzo V
Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.
Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis
Black N, Stockings E, Campbell G, Tran LT, Zagic D, Hall WD, Farrell M and Degenhardt L
Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
Myrcene and terpene regulation of TRPV1
Jansen C, Shimoda LMN, Kawakami JK, Ang L, Bacani AJ, Baker JD, Badowski C, Speck M, Stokes AJ, Small-Howard AL and Turner H
Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the component myrcene have been suggested as pain therapeutics, we screened terpenes found in for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by -mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the whole-cell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of I and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non- plant-derived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.
Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of cannabidiol (CBD)
Good P, Haywood A, Gogna G, Martin J, Yates P, Greer R and Hardy J
Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.
Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report
Hegazy O and Platnick H
Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety. Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects. In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.
A Warning against the Negligent Use of Cannabidiol in Professional and Amateur Athletes
Lachenmeier DW and Diel P
Cannabidiol (CBD) is a non-psychoactive cannabinoid, widely marketed to athletes for claimed effects such as decreased anxiety, fear memory extinction, anti-inflammatory properties, relief of pain and for post-exercise recovery. The World Anti-Doping Agency (WADA) has excluded CBD from its list of prohibited substances. Nevertheless, caution is currently advised for athletes intending to use the compound-except CBD, all other cannabinoids are still on the prohibited list. CBD products, specifically non-medicinal, so-called full-spectrum cannabis extracts, may contain significant levels of these substances, but also contaminations of tetrahydrocannabinol (THC) (>2.5 mg/day in >30% of products on the German market) potentially leading to positive doping tests. Labelled claims about CBD content and absence of THC are often false and misleading. Contaminations with the psychoactive THC can result in adverse effects on cognition and, in general, the safety profile of CBD with respect to its toxicity is a controversial topic of discussion. For these reasons, we would currently advise against the use of over-the-counter CBD products, especially those from dubious internet sources without quality control.
Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD: A Randomized, Double-Blind Trial
Nitecka-Buchta A, Nowak-Wachol A, Wachol K, Walczyńska-Dragon K, Olczyk P, Batoryna O, Kempa W and Baron S
(1) Background: The healing properties of cannabidiol (CBD) have been known for centuries. In this study, we aimed to evaluate the efficiency of the myorelaxant effect of CBD after the transdermal application in patients with myofascial pain. (2) Methods: The Polish version of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD Ia and Ib) was used. A total of 60 patients were enrolled in the study and were randomly divided into two groups: Group1 and Group2. The average age in Group1 was 23.2 years (SD) = 1.6 years) and in Group2, it was 22.6 years (SD = 1.86). This was a parallel and double-blind trial. Group1 received CBD formulation, whereas Group2 received placebo formulation for topical use. The masseter muscle activity was measured on days 0 and 14, with surface electromyography (sEMG) (Neurobit Optima 4, Neurobit System, Gdynia, Poland). Pain intensity in VAS (Visual Analogue Scale) was measured on days 0 and 14. (3) Results: in Group1, the sEMG masseter activity significantly decreased (11% in the right and 12.6% in the left masseter muscles). In Group2, the sEMG masseter activity was recorded as 0.23% in the right and 3.3% in the left masseter muscles. Pain intensity in VAS scale was significantly decreased in Group1: 70.2% compared to Group2: 9.81% reduction. Patients were asked to apply formulation twice a day for a period of 14 days. (4) Conclusion: The application of CBD formulation over masseter muscle reduced the activity of masseter muscles and improved the condition of masticatory muscles in patients with myofascial pain.
Short- and Long-Term Effects of Cannabis on Headache and Migraine
Cuttler C, Spradlin A, Cleveland MJ and Craft RM
Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs flower), delta-9-tetrahydrocannabinol, cannabidiol, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from Strainprint, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine. There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects. PERSPECTIVE: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.
Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial
Urbi B, Broadley S, Bedlack R, Russo E and Sabet A
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3-5 years post diagnosis. The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS. Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS. There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain. However, a clinical trial in pALS with these objectives has not been conducted.
Cannabis and cannabinoids
Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis
Abrantes De Lacerda Almeida T, Santos MV, Da Silva Lopes L, Goel G, Leonardo De Freitas R, De Medeiros P, Crippa JA and Machado HR
. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage. . 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted. . Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol. . The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.
[Cannabis-derived medicines for the treatment of chronic pain : Problems resulting from medical appraisals in the experience of the Medical Advisory Board of the Statutory Health Insurance Funds North]
Heidbreder M and van Treeck B
On March 10th 2017, the law amending narcotic and other regulations was expanded, thereby allowing physicians, irrespective of their specialization, to prescribe cannabis-derived medicines as magistral formulas or proprietary medicinal products at the expense of the German statutory health insurance (GKV). First prescription requires approval from the respective health insurance, which in turn commissions the Medical Advisory Board of the Statutory Health Insurance Funds (MDK) to prepare a medico-legal report.
The effectiveness of self-directed medical cannabis treatment for pain
Li X, Vigil JM, Stith SS, Brockelman F, Keeling K and Hall B
The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief. Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis' effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was -3.10 points on a 0-10 visual analogue scale (SD = 2.16, d = 1.55, p < .001). Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain. These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.
Medical cannabis and cannabinoids in rheumatology: where are we now?
Sarzi-Puttini P, Batticciotto A, Atzeni F, Bazzichi L, Di Franco M, Salaffi F, Marotto D, Ceribelli A, Ablin JN and Hauser W
: Clinicians involved in pain management can finally include cannabis or cannabis-related products in their therapeutic armamentarium as a growing number of countries have approved them for pain relief. Despite the several benefits attributed to analgesic, anti-inflammatory and immunomodulatory properties of cannabinoids, there are still significant areas of uncertainty concerning their use in many fields of medicine. The biosynthesis and inactivation of cannabinoids are regulated by a complex signaling system of cannabinoid receptors, endocannabinoids (the endogenous ligands of cannabinoid receptors) and enzymes, with a variety of interactions with neuroendocrinological and immunological systems. : A review of studies carried out during clinical development of cannabis and cannabis medical products in systemic rheumatic diseases was performed, highlighting the aspects that we believe to be relevant to clinical practice. : The growing public opinion, pushing toward the legalization of the use of cannabis in chronic pain and various rheumatological conditions, makes it necessary to have educational programs that modify the concerns and widespread preconceptions related to this topic in the medical community by increasing confidence. More extensive basic and clinical research on the mechanisms and clinical utility of cannabis and derivatives in various diseases and their long-term side effects is necessary.
Benefit of Tetrahydrocannabinol versus Cannabidiol for Common Palliative Care Symptoms
Casarett DJ, Beliveau JN and Arbus MS
To determine the relative contributions of tetrahydrocannabinol (THC) and cannabidiol (CBD) to patients' self-ratings of efficacy for common palliative care symptoms. This is an electronic record-based retrospective cohort study. Model development used logistic regression with bootstrapped confidence intervals (CIs), with standard errors clustered to account for multiple observations by each patient. This is a national Canadian patient portal. A total of 2,431 patients participated. Self-ratings of efficacy of cannabis, defined as a three-point reduction in neuropathic pain, anorexia, anxiety symptoms, depressive symptoms, insomnia, and post-traumatic flashbacks. We included 26,150 observations between October 1, 2017 and November 28, 2018. Of the six symptoms, response was associated with increased THC:CBD ratio for neuropathic pain (odds ratio [OR]: 3.58; 95% CI: 1.32-9.68;  = 0.012), insomnia (OR: 2.93; 95% CI: 1.75-4.91;  < 0.001), and depressive symptoms (OR: 1.63; 95% CI: 1.07-2.49;  = 0.022). Increased THC:CBD ratio was not associated with a greater response of post-traumatic stress disorder (PTSD)-related flashbacks (OR: 1.43; 95% CI: 0.60-3.41;  = 0.415) or anorexia (OR: 1.61; 95% CI: 0.70-3.73;  = 0.265). The response for anxiety symptoms was not significant (OR: 1.13; 95% CI: 0.77-1.64;  = 0.53), but showed an inverted U-shaped curve, with maximal benefit at a 1:1 ratio (50% THC). These preliminary results offer a unique view of real-world medical cannabis use and identify several areas for future research.
The potential role of cannabinoids in dermatology
Sheriff T, Lin MJ, Dubin D and Khorasani H
Cannabis is increasingly being used world-wide to treat a variety of dermatological conditions. Medicinal cannabis is currently legalized in Canada, 31 states in America and 19 countries in Europe. The authors reviewed the literature on the pharmacology and use of cannabinoids in treating a variety of skin conditions including acne, atopic dermatitis, psoriasis, skin cancer, pruritus, and pain. Cannabinoids have demonstrated anti-inflammatory, antipruritic, anti-ageing, and antimalignancy properties by various mechanisms including interacting with the newly found endocannabinoid system of the skin thereby providing a promising alternative to traditional treatments.
[High-dose dronabinol treatment vs. medicinal cannabis flowers]
Wendelmuth C and Gastmeier K
This article reports a case of pronounced, chronic lumboischialgia, which was not satisfactorily controlled by conventional analgesic treatment. The level of pain under high-dose dronabinol treatment with oral and inhalative administration as well as the way to reimburse the cost of medicinal cannabis flowers, the treatment success and criteria of the economic prescription procedure are presented.
Cannabidiol (CBD) use in psychiatric disorders: A systematic review
Bonaccorso S, Ricciardi A, Zangani C, Chiappini S and Schifano F
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different activity compared with the psychotomimetic THC. Most typically, CBD is reported to be used in some medical conditions, including chronic pain. Conversely, the main aim of this systematic review is to assess and summarise the available body of evidence relating to both efficacy and safety of CBD as a treatment for psychiatric disorders, alone and/or in combination with other treatments. Eligible studies included randomized controlled trials (RCT) assessing the effect of CBD in a range of psychopathological conditions, such as substance use; psychosis, anxiety, mood disturbances, and other psychiatric (e.g., cognitive impairment; sleep; personality; eating; obsessive-compulsive; post-traumatic stress/PTSD; dissociative; and somatic) disorders. For data gathering purposes, the PRISMA guidelines were followed. The initial search strategy identified some n = 1301 papers; n = 190 studies were included after the abstract's screening and n = 27 articles met the inclusion criteria. There is currently limited evidence regarding the safety and efficacy of CBD for the treatment of psychiatric disorders. However, available trials reported potential therapeutic effects for specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Further large-scale RCTs are required to better evaluate the efficacy of CBD in both acute and chronic illnesses, special categories, as well as to exclude any possible abuse liability.
High-Frequency Medical Cannabis Use Is Associated With Worse Pain Among Individuals With Chronic Pain
Boehnke KF, Scott JR, Litinas E, Sisley S, Williams DA and Clauw DJ
Cannabis is widely used for chronic pain. However, there is some evidence of an inverse dose-response relationship between cannabis effects and pain relief that may negatively affect analgesic outcomes. In this cross-sectional survey, we examined whether daily cannabis use frequency was associated with pain severity and interference, quality of life measures relevant to pain (eg, anxiety and depressive symptoms), and cannabis use preferences (administration routes and cannabinoid ratio). Our analysis included 989 adults who used cannabis every day for chronic pain. Participant use was designated as light, moderate, and heavy (1-2, 3-4, and 5 or more cannabis uses per day, respectively). The sample was also subgrouped by self-reported medical-only use (designated MED, n = 531, 54%) versus medical use concomitant with a past-year history of recreational use (designated MEDREC, n = 458, 46%). In the whole sample, increased frequency of use was significantly associated with worse pain intensity and interference, and worse negative affect, although high-frequency users also reported improved positive affect. Subgroup analyses showed that these effects were driven by MED participants. Heavy MED participant consumption patterns showed greater preference for smoking, vaporizing, and high tetrahydrocannabinol products. In contrast, light MED participants had greater preference for tinctures and high cannabidiol products. Selection bias, our focus on chronic pain, and our cross-sectional design likely limit the generalizability of our results. Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as lower risk cannabis use behaviors among MED participants. Future longitudinal studies are needed to examine how high frequency of cannabis use interacts with potential therapeutic benefits. PERSPECTIVE: Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as safer use behaviors (eg, preference for cannabidiol and noninhalation administration routes). These trends highlight the need for developing cannabis use guidelines for clinicians to better protect patients using cannabis.
Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends
Reece AS and Hulse GK
Rising Δ9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure. Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down's syndrome, ventricular septal defect, and patent ductus arteriosus rose, and along with central nervous system, cardiovascular, genitourinary, respiratory, chromosomal, and musculoskeletal defects rose 5 to 37 times faster than the birth rate (3.3%) to generate an excess of 11 753 (22%) major anomalies. Cannabis was the only drug whose use grew from 2000 to 2014 while pain relievers, cocaine, alcohol, and tobacco did not. The correlation of cannabis use with major defects in 2014 (2019 dataset) was = .77, = .0011. Multiple cannabinoids were linked with summary measures of congenital anomalies and were robust to multivariate adjustment.
A systematic review of cannabidiol dosing in clinical populations
Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ and O'Sullivan SE
Cannabidiol (CBD) is a cannabis-derived medicinal product with potential application in a wide-variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts.
Clinicians' Guide to Cannabidiol and Hemp Oils
VanDolah HJ, Bauer BA and Mauck KF
Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.
Cannabis's chemical synergies
Worth T
[Medical Cannabis-Related Relapse in a Patient with a History of Alcohol Abuse]
Flöther L, Peitek K, Bucher M and Benndorf RA
In this report, a 60-year old patient with a history of mixed nociceptive and neuropathic chronic pain after successful removal of oral squamous cell cancer is described who received outpatient pain treatment in our clinic. Moreover, the patient presented with a history of alcohol abuse as well as anorexia and weight loss.
Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis
Zhou T, Ahmad TK, Alrushaid S, Pozdirca M, Ethans K, Intrater H, Le T, Burczynski F, Kong J and Namaka M
There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP). Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 - tetrahydrocannabinol/cannabidiol) treatment. Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production. Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials.
The Endocannabinoid System and its Modulation by Cannabidiol (CBD)
Corroon J and Felice JF
The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.
leaf extract facilitates oligodendrocyte development
Kim JY, Yoon JY, Sugiura Y, Lee SK, Park JD, Song GJ and Yang HJ
Treatment of multiple sclerosis is effective when anti-inflammatory, neuroprotective and regenerative strategies are combined. () has anti-inflammatory, anti-oxidative properties, which may be beneficial for multiple sclerosis. However, there have been no reports on the effects of on myelination, which is critical for regenerative processes. To know whether benefits myelination, we checked differentiation and myelination of oligodendrocytes (OLs) in various primary culture systems treated with leaf EtOH extracts or control. extracts increased the OL membrane size in the mixed glial and pure OL precursor cell (OPC) cultures and changed OL-lineage gene expression patterns in the OPC cultures. Western blot analysis of -treated OPC cultures showed upregulation of MBP and phosphorylation of ERK1/2. In myelinating cocultures, extracts enhanced OL differentiation, followed by increased axonal contacts and myelin gene upregulations such as Myrf, CNP and PLP. Phytochemical analysis by LC-MS/MS identified multiple components from extracts, containing bioactive molecules such as quercetin, cannabidiol, etc. Our results suggest extracts enhance OL differentiation, followed by an increase in membrane size and axonal contacts, thereby indicating enhanced myelination. In addition, we found that extracts contain multiple bioactive components, warranting further studies in relation to finding effective components for enhancing myelination.
A Hemp oil, CBD, and Marijuana Primer: Powerful Pain, Insomnia, and Anxiety-relieving Tools!
Teitelbaum J
No Abstract Available.
Cannabis and Neuropsychiatric Disorders: An Updated Review
Chayasirisobhon S
Cannabis plant has the scientific name called Cannabis sativa L. Cannabis plant has many species, but there are three main species including Cannabis sativa, Cannabis indica and Cannabis ruderalis. Over 70 compounds isolated from cannabis species are called cannabinoids (CBN). Cannabinoids produce over 100 naturally occurring chemicals. The most abundant chemicals are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is psychotropic chemical that makes people feel "high" while CBD is nonpsychotropic chemical. However, cannabinoid chemicals are not found only in the cannabis plant, they are also produced by the mammalian body, called endocannabinoids and in the laboratory, called synthesized cannabinoids. Endocannabinoids are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the mammalian central nervous system including brain and peripheral nervous system. There are at least two types of endocannabinoid receptors (CB1 and CB2) which are G-protein coupled receptors. CB1 receptors are particularly abundant in the frontal cortex, hippocampus, basal ganglia, hypothalamus and cerebellum, spinal cord and peripheral nervous system. They are present in inhibitory GABA-ergic neurons and excitatory glutamatergic neurons. CB2 receptor is most abundantly found on cells of the immune system, hematopoietic cells and glia cells. CB2 is mainly expressed in the periphery under normal healthy condition, but in conditions of disease or injury, this upregulation occurs within the brain, and CB2 is therefore expressed in the brain in unhealthy states. Cannabis and cannabinoid are studied in different medical conditions. The therapeutic potentials of both cannabis and cannabinoid are related to the effects of THC, CBD and other cannabinoid compounds. However, the "high" effect of THC in cannabis and cannabinoid may limit the clinical use, particularly, the study on the therapeutic potential of THC alone is more limited. This review emphasizes the therapeutic potential of CBD and CBD with THC. CBD has shown to have benefit in a variety of neuropsychiatric disorders including autism spectrum disorder, anxiety, psychosis, neuropathic pain, cancer pain, HIV, migraine, multiple sclerosis, Alzheimer disease, Parkinson disease, Huntington disease, hypoxic-ischemic injury and epilepsy. CBD is generally well tolerated. Most common adverse events are diarrhea and somnolence. CBD also shows significantly low abuse potential.
A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain
Überall MA
The 20% prevalence of chronic pain in the general population is a major health concern given the often profound associated impairment of daily activities, employment status, and health-related quality of life in sufferers. Resource utilization associated with chronic pain represents an enormous burden for healthcare systems. Although analgesia based on the World Health Organization's pain ladder continues to be the mainstay of chronic pain management, aside from chronic cancer pain or end-of-life care, prolonged use of non-steroidal anti-inflammatory drugs or opioids to manage chronic pain is rarely sustainable. As the endocannabinoid system is known to control pain at peripheral, spinal, and supraspinal levels, interest in medical use of cannabis is growing. A proprietary blend of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as the principal cannabinoids is formulated as an oromucosal spray (USAN name: nabiximols) and standardized to ensure quality, consistency and stability. This review examines evidence for THC:CBD oromucosal spray (nabiximols) in the management of chronic pain conditions. Cumulative evidence from clinical trials and an exploratory analysis of the German Pain e-Registry suggests that add-on THC:CBD oromucosal spray (nabiximols) may have a role in managing chronic neuropathic pain, although further precise clinical trials are required to draw definitive conclusions.
The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study
Bar-Sela G, Zalman D, Semenysty V and Ballan E
Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients. The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline. Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients' self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.
Aplicaciones terapéuticas por acción de los cannabinoides
Plancarte-Sánchez R, Mansilla-Olivares A, De Los Reyes-Pacheco VA and Meneses-González F
The interest on cannabinoids became evident between the 1940 and 1950 decades. Although the active substance of the plant was not known, a series of compounds with cannabinomimetic activity were synthesized, which were investigated in animals and clinically. The most widely tested was Δ6a, 10a-THC hexyl. Δ6a, 10a-THC dimethylheptyl (DMHP) antiepileptic effects were studied in several children, with positive results being obtained in some cases. DMHP differs from sinhexyl in that its side chain is DMHP instead of n-hexyl. The first cannabinoid isolated from Cannabis sativa was cannabinol, although its structure was correctly characterized several years later. Cannabidiol was isolated some years later and was subsequently characterized by Mechoulam and Shvo. In 2013, the National Academy of Medicine and the Faculty of Medicine of the National Autonomous University of Mexico, through the Seminar of Studies on Entirety, decided to carry out a systematic review on a subject that is both complex and controversial: the relationship between marijuana and health. In recent years, studies have been conducted with cannabis in several diseases: controlled clinical trials on spasticity in multiple sclerosis and spinal cord injury, chronic, essentially neuropathic, pain, movement disorders (Gilles de Latourette, dystonia, levodopa dyskinesia), asthma and glaucoma, as well as non-controlled clinical trials on Alzheimer's disease, neuroprotection, intractable hiccups, epilepsy, alcohol and opioid dependence and inflammatory processes.
Cannabinoids, Pain, and Opioid Use Reduction: The Importance of Distilling and Disseminating Existing Data
Hutchison KE, Hagerty SL, Galinkin J, Bryan AD and Bidwell LC
The high prevalence of chronic pain conditions combined with an over-reliance on opioid prescriptions has resulted in an opioid epidemic and a desperate need for solutions. There is some debate about whether cannabis might play a role in addressing chronic pain conditions as well as the opioid epidemic. Recent surveys suggest that a large number of people are using cannabis as a treatment for pain and to reduce use of opioids, and cannabis-derived products demonstrate at least modest efficacy in the treatment of pain in randomized controlled trials. In addition, surveillance studies from countries that have approved the use of Sativex, which is a cannabis-based product, have demonstrated that a combination of Δ9-tetrahydrocannabinol and cannabidiol has low potential for harm, is well tolerated, and is helpful to patients. Given the number of people in the United States who are already using cannabis to manage pain and opioid use in state-regulated markets, it is imperative to conduct additional research in these areas, and to disseminate information on how to minimize harm and maximize any benefits of using cannabinoids to mitigate pain and reduce opioid use. The purpose of this article is to call attention to the fact that cannabis is being used in the management of chronic pain. Thus, this article also provides a set of guidelines on how to approach using cannabis to treat pain.
Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review
Eskander JP, Spall J, Spall A, Shah RV and Kaye AD
Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.
Pharmacology of Medical Cannabis
Amin MR and Ali DW
The Cannabis plant has been used for many of years as a medicinal agent in the relief of pain and seizures. It contains approximately 540 natural compounds including more than 100 that have been identified as phytocannabinoids due to their shared chemical structure. The predominant psychotropic component is Δ-tetrahydrocannabinol (Δ-THC), while the major non-psychoactive ingredient is cannabidiol (CBD). These compounds have been shown to be partial agonists or antagonists at the prototypical cannabinoid receptors, CB1 and CB2. The therapeutic actions of Δ-THC and CBD include an ability to act as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds and as protective agents in neurodegeneration. However, there is a lack of well-controlled, double blind, randomized clinical trials to provide clarity on the efficacy of either Δ-THC or CBD as therapeutics. Moreover, the safety concerns regarding the unwanted side effects of Δ-THC as a psychoactive agent preclude its widespread use in the clinic. The legalization of cannabis for medicinal purposes and for recreational use in some regions will allow for much needed research on the pharmacokinetics and pharmocology of medical cannabis. This brief review focuses on the use of cannabis as a medicinal agent in the treatment of pain, epilepsy and neurodegenerative diseases. Despite the paucity of information, attention is paid to the mechanisms by which medical cannabis may act to relieve pain and seizures.
Preclinical and Clinical Evidence Supporting Use of Cannabidiol in Psychiatry
Calapai G, Mannucci C, Chinou I, Cardia L, Calapai F, Sorbara EE, Firenzuoli B, Ricca V, Gensini GF and Firenzuoli F
Cannabidiol (CBD) is a major chemical compound present in . CBD is a nonpsychotomimetic substance, and it is considered one of the most promising candidates for the treatment of psychiatric disorders.
The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities
Xu DH, Cullen BD, Tang M and Fang Y
Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial.
A Balanced Approach for Cannabidiol Use in Chronic Pain
Argueta DA, Ventura CM, Kiven S, Sagi V and Gupta K
Cannabidiol (CBD), the major non-psychoactive constituent of L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations. In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.
Cannabidiol prescription in clinical practice: an audit on the first 400 patients in New Zealand
Gulbransen G, Xu W and Arroll B
Cannabidiol (CBD) is the non-euphoriant component of cannabis. In 2017, the New Zealand Misuse of Drugs Regulations (1977) were amended, allowing doctors to prescribe CBD. Therapeutic benefit and tolerability of CBD remains unclear.
The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis
Rabgay K, Waranuch N, Chaiyakunapruk N, Sawangjit R, Ingkaninan K and Dilokthornsakul P
To determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events.
Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome
Yin HY, Hadjokas N, Mirchia K, Swan R and Alpert S
To report an unusual presentation of commercial cannabidiol (CBD) oil-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS-TEN).
A Case of Vaping TCH Oil Leading to Vaping Associated Pulmonary Injury: Our Approach to Its Diagnosis, Management, and Recommendations
Singh A, Tan Q, Saccone NM and Lindner DH
Vaping's popularity has grown exponentially since its introduction to the US market in 2003. Its use has sky-rocketed since the unveiling of the vaping pods in 2017 which may account for the advent of the vaping related illnesses we are now seeing. Substances such as nicotine solution, tetrahydrocannabinol (THC) oil, cannabidiol (CBD) oil, and butane hash oil (BHC) packaged in cartridges available in various flavors and concentrations are aerosolized by the heating of metal coils in the e-cigarette/vaping devices. Cases from all over the country have recently been coming to light in which vaping has led to severe acute pulmonary disease or vaping-associated-pulmonary-injury (VAPI). A vast majority of the presenting patients in the reported cases have required hospitalization and intensive care, needing supplemental oxygen and even endotracheal intubation and mechanical ventilation. 98% of patients present with respiratory symptoms (dyspnea, hypoxia, chest pain, cough, hemoptysis), 81% of patients have gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), and 100% of patients have constitutional symptoms such as fever, chills, and fatigue/malaise on presentation. Although based on history and clinical presentation it is reasonable to have a high suspicion for VAPI, diagnostic workup to rule out alternative underlying causes such as infection, malignancy, or autoimmune process should be performed before establishing the diagnosis. Computed Tomography (CT) scans of the chest have predominantly shown ground-glass opacity in the lungs, often with areas of lobular or subpleural sparing. Although lung biopsies have been performed on a relatively low number of cases, lung injury patterns so far have shown acute fibrinous pneumonitis, diffuse alveolar hemorrhage, or organizing pneumonia, usually bronchiolocentric, and accompanied by bronchiolitis. Treatment plans that have led to clinical improvement in the reported cases center around high-dose systemic steroids, although there are a lack of data regarding the best regimen and the absolute need for corticosteroids. The role of antibiotics appears to be limited once infection has definitively been ruled out. We present the case of a young male who vaped THC oil and developed severe acute pulmonary injury requiring mechanical ventilation and showed a remarkable response to high dose steroid therapy with improvement in clinical symptoms and resolution of diffuse ground glass opacity on repeat HRCT scan.
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