The health benefits and risks of cannabis

People have promoted the health benefits of cannabis/marijuana for decades. That has been a factor in the loosening of marijuana use restrictions in the United States in recent years. And yet, restrictions at the Federal and some State levels remain intact.

What does research actually say about the benefits and risks of medical cannabis? Is there actual evidence or are the reports largely anecdotal?

Featured articles (these articles have been added to Science Primary Literature):

*Amin, M. R., & Ali, D. W. (2019). Pharmacology of medical cannabis. Advances in Experimental Medicine and Biology, 1162, 151-165. [Cited by]

The Cannabis plant has been used for many 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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-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 Δ9-THC or CBD as therapeutics. Moreover, the safety concerns regarding the unwanted side effects of Δ9-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.”

*Coughlin, L. N., Ilgen, M. A., Jannausch, M., Walton, M. A., & Bohnert, K. M. (2021). Progression of cannabis withdrawal symptoms in people using medical cannabis for chronic pain. Addiction, 116(8), 2067-2075. [Cited by]

“Background and aims: Research from cohorts of individuals with recreational cannabis use indicates that cannabis withdrawal symptoms are reported by more than 40% of those using regularly. Withdrawal symptoms are not well understood in those who use cannabis for medical purposes. Therefore, we prospectively examined the stability of withdrawal symptoms in individuals using cannabis to manage chronic pain.

Design, Setting, Participants: Using latent class analysis (LCA) we examined baseline cannabis withdrawal to derive symptom profiles. Then, using latent transition analysis (LTA) we examined the longitudinal course of withdrawal symptoms across the time points. Exploratory analyses examined demographic and clinical characteristics predictive of withdrawal class and transitioning to more or fewer withdrawal symptoms over time.

A cohort of 527 adults with chronic pain seeking medical cannabis certification or re-certification was recruited between February 2014 and June 2015. Participants were recruited from medical cannabis clinic waiting rooms in Michigan, USA. Participants were predominantly white (82%) and 49% identified as male, with an average age of 45.6 years (standard deviation = 12.8).

Measurements: Baseline, 12-month and 24-month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist–revised.

Findings: A three-class LCA model including a mild (41%), moderate (34%) and severe (25%) symptom class parsimoniously represented withdrawal symptoms experienced by people using medical cannabis. Stability of withdrawal symptoms using a three-class LTA at 12 and 24 months ranged from 0.58 to 0.87, with the most stability in the mild withdrawal class. Younger age predicted greater severity and worsening of withdrawal over time.

Conclusions: Adults with chronic pain seeking medical cannabis certification or re-certification appear to experience mild to severe withdrawal symptoms. Withdrawal symptoms tend to be stable over a 2-year period, but younger age is predictive of worse symptoms and of an escalating withdrawal trajectory.

*Ebbert, J. O., Scharf, E. L., & Hurt, R. T. (2018). Medical cannabis. Mayo Clinic Proceedings, 93(12), 1842-1847. [HTML] [Cited by]

“Medicolegal realities surrounding “medical marijuana” or “medical cannabis” are rapidly evolving in the United States. Clinicians are increasingly being asked by patients to share information about or certify them for medical cannabis. In order to engage in informed discussions with patients or be comfortable certifying them in states with medical cannabis laws, clinicians may benefit from an understanding of the current state of medical knowledge about medical cannabis. Intended for the generalist and subspecialist, this review provides an overview of the legal status, pharmacology, benefits, risks, and abuse liability of medical cannabis along with a general framework for counseling patients.”

*Li, X., Vigil, J. M., Stith, S. S., Brockelman, F., Keeling, K., & Hall, B. (2019). The effectiveness of self-directed medical cannabis treatment for pain. Complementary Therapies in Medicine, 46, 123-130. [Cited by]

“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.

*Luque, J. S., Okere, A. N., Reyes-Ortiz, C., & Williams, P. M. (2021). Mixed methods study of the potential therapeutic benefits from medical cannabis for patients in Florida. Complementary Therapies in Medicine, 57, 102669. [Cited by]

“Objectives: To evaluate medical marijuana patients’ perceptions of therapeutic benefits for self-reported medical conditions.

Design: The study was a concurrent mixed methods study with adult medical marijuana patients. Survey data were collected using a web-based survey, and interviews were conducted in person or over the phone.

Setting: The study recruited 196 medical marijuana patients to complete surveys and 13 patients to participate in qualitative interviews in Florida.

Measures: A validated patient survey was distributed via Florida medical marijuana social media groups to examine the therapeutic benefits of the cannabis plant for medical conditions and overall well-being. Concurrently, qualitative interviews were conducted to understand barriers and facilitators to accessing medical cannabis and explore preferences for different forms and strains, as well as any unexpected side effects.

Results: Patients used medical cannabis for relief of chronic pain or depression, followed by arthritis and nausea. Survey results indicated 89% of patients reported “great relief” for their medical condition. Over 76% of patients reported a score of 8 or higher on a 10-point scale that their medical condition had improved, and over 68% reported a score of 8 or higher that medical cannabis had reduced their pain. Interviews indicated medical cannabis was effective for pain relief and reducing the use of prescription medicines, but the drug was perceived as too expensive.

Conclusions: Medical marijuana patients were positive about the health benefits they received and the fact they were able to reduce or eliminate many prescription medications; however, there were concerns about the costs.

*Safety and efficacy of medicinal cannabis in the treatment of fibromyalgia: A systematic review. (2021). The Journal of Alternative and Complementary Medicine, 27(3), 198-213. [Cited by]

“Background: Fibromyalgia (FMS) is a complex condition that is characterized by various pain syndromes and fatigue, among other symptoms experienced. Current medical treatment of FMS involves both pharmacological and nonpharmacological approaches, but often with ineffective outcomes. Medicinal cannabis has the potential to be a therapeutic option for patients with FMS due to the positive research in chronic pain management. In addition, it has been found to have fewer adverse effects compared with currently available pain medications. This literature review aims at answering whether medicinal cannabis is reported to be safe and effective for the treatment of pain and symptomology experienced by people with FMS.

Methods: A systematic review was conducted on human trials utilizing cannabis in FMS. MEDLINE, Embase, CINAHL, AMED, Scopus, and Cochrane CENTRAL were used for databases search, and mesh terms were used for cannabis and FMS. The search was limited to studies conducted from 2000 to 2020.

Results: From the 181 citations identified, 10 studies were included after title, abstract, and full text screening occurred. A total of 1136 patients (intervention n = 945, control n = 108, crossover n = 83) participated in the 10 studies ranging from 9 to 383 patients (mean = 114, median = 36). Of these studies, there were three randomized controlled trials, six observational studies, and one study that compared the management of chronic pain patients with FMS patients. Cannabis was found to be safe and well tolerated in FMS. The main adverse events identified included feeling “high,” dizziness/vertigo, dry mouth, cough, red eyes, and drowsiness with no serious adverse events reported.

Conclusions: This literature review identified that medical cannabis may be beneficial for some people with FMS. Further studies are required to confirm its efficacy, what type of cannabis is the most effective form to use, and what assessment tools need to be utilized to understand how to quantify clinical outcomes.

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