This Month in Psychopharmacology

Evaluating the Evidence for Cannabis as a Therapeutic Option: Focus on Chronic Pain and PTSD

As the medicinal use of cannabis becomes increasingly accepted and legal--at least at the state level--a major concern for the medical community is: what is the evidence regarding the efficacy and safety of cannabis as a treatment for medical and psychiatric disorders? Two recent reviews, commissioned by the Veterans Health Administration and funded by the US Department of Veterans Affairs, addressed this issue specifically for chonic pain and posttraumatic stress disorder (PTSD).

Nugent et al. (2017) analyzed English-language intervention and observational studies of plant-based cannabis preparations for treating chronic pain, as well as studies of the harms of cannabis in chronic pain and general adult populations. They identified 27 chronic pain trials that, collectively, demonstrated low-strength evidence that cannabis use may reduce neuropathic pain, with insufficient evidence that it improves any other types of chronic pain. There was a possible indication of increased short-term adverse effects, but not all studies showed this. In studies of the general population, there was insufficient evidence to determine the long-term cardioavscular effects of cannabis smoking, and low-strength evidence that it is not associated with increased risk for lung, neck, or head cancer. There was consistent evidence of an increased risk for acute psychotic symptoms, cognitive impairment, and motor vehicle accidents.

O'Neil et al. (2017) assessed the English-language literature on the use of cannabis as a treatment for PTSD. They found no randomized trials and only 3 observational studies and 2 systematic reviews. Collectively, these studies provided insufficient evidence to assess the benefits or harms of the use of cannabis in patients with PTSD. They did note the existence of ongoing studies, 2 of which are randomized trials.

The results of these two studies are consistent with other recent analyses, which suggest that there is moderate evidence to support the use of cannabis for some types of chronic pain, but not enough data to determine if there is efficacy for PTSD (Whiting et al., 2015; Koppel et al., 2014). The aggregate data also support the potential negative effects of cannabis use, including short-term cognitive impairment (Volkow et al., 2016; Schreiner and Dunn, 2012), increased risk of acute psychotic symptoms (Sherif et al., 2016), increased risk for psychosis in at-risk populations (Gage et al., 2016; Volkow et al., 2016), and increased risk of relapse in psychotic disorders (Schoeler et al., 2016).

A complication when evaluating the effects of cannabis is the fact that “cannabis” is not one thing. In fact, there are as many as 500 chemicals within the cannabis plant, and approximately 60 to 100 of those are cannabinoids that potentially compete with or mimic the effects of the endogenous cannabinoids (Greydanus et al., 2015). Each strain of cannabis may contain a different combination of cannabinoids, some of which may be agonists (e.g., tetrahydrocannabinol, partial agonist) while others are antagonists and still others don't seem to bind to any cannabinoid receptors (e.g., cannabidiol). In addition, the extraction process can affect potencies; thus, it can be difficult to predict what the effects will be of any particular cananbis product. This is important to consider when one evaluates the collective research, which may include studies of a variety of cannabis preparations. Likewise, the published literature about the effects of cannabis may not inform clinicians well if the products that a patient obtains at a dispensary are different than those that have been studied.



     Interested in learning more about cannabis and its effects? NEI Members can access:

Animation:
Cannabis and the Developing Brain, Part 1: The Endocannabinoid System
Animation:
Cannabis and the Developing Brain, Part 2: Consequences of Heavy Use
Encore Presentation:
Marijuana: Substance of Abuse or Therapeutic Option?

References

Gage SH, Hickman M, Zammit S. Association between cannabis and psychosis: epidemiologic evidence. Biol Psychiatry 2016;79:549-56.

Greydanus DE, Kaplan G, Baxter LE et al. Cannabis: the never-ending, nefarious nepenthe of the 21st century: what should the clinician know? Disease-a-Month 2016;6:118-75.

Koppel BS, Brust JC, Bronstein J et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1556-63.

Nugent SM, Morasco BJ, O'Neil ME et al. The effects of cannabis among adults with chronic pain and an overview of general harms. Ann Intern Med 2017;doi:10.7326/M17-0155.

O'Neil ME, Nugent SM, Morasco BJ et al. Benefits and harms of plant-based cannabis for posttraumatic stress disorder. Ann Intern Med 2017;doi:10.7326M17-0477.

Schoeler T, Monk A, Sami MB et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry 2016;3(3):215-25.

Schreiner AM, Dunn ME. Residual effects of cannabis use on neurocognitive performance after prolonged abstinence: a meta-analysis. Psychopharmacology 2012;20(5):420-9.

Sherif M, Radhakrishnan R, D'Souza DC, Ranganathan M. Human laboratory stuedies on cannabinoids and psychosis. Biol Psychiatry 2016;79:526-38.

Volkow ND, Swanson JM, Evins E et al. Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review. JAMA Psychiatry 2016;73(3):292-7.

Whiting PF, Wolff RF, Deshpande S et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313(24):2456-73.