By Austin Ulrich, PharmD, BCACP

Clinical Pharmacist Practitioner, UpStream Pharmaceutical Care, Greensboro, NC

SYNOPSIS: Using cannabis-based medicine often exposes patients to delta-9-tetrahydrocannabinol (THC), which is associated with psychotic symptoms. THC also can cause lightheadedness, dizziness, and thinking or perception disorder in older adults.

SOURCE: Velayudhan L, McGoohan KL, Bhattacharyya S. Evaluation of THC-related neuropsychiatric symptoms among adults aged 50 years and older: A systematic review and metaregression analysis. JAMA Netw Open 2021;4:e2035913.

In recent years, the use of cannabis-based medicines (CBMs) has increased substantially, with a growing number of U.S. states allowing CBMs for medical conditions.1 These conditions often affect older adults and include a variety of chronic diseases, such as Parkinson’s disease, Alzheimer’s disease, cancer pain, and chemotherapy-induced nausea and vomiting. Active ingredients in cannabis include delta-9-tetrahydrocannabinol (THC), which can induce psychotic symptoms, memory impairment, and anxiety, and cannabidiol (CBD), which is not addictive and can possibly ameliorate the psychotic effects of THC.2 Although investigations of CBMs continue, these studies generally include small sample sizes and the authors use different formulations of CBMs (consisting of various combinations of THC and CBD), often preventing clear conclusions about efficacy of these treatments.3 While the occurrence of psychotic symptoms from THC-containing CBMs is well established in younger individuals, effects on older adults are less understood.1,4

In a recent systematic review and metaregression analysis, Velayudhan et al evaluated randomized studies (published from January 1990 to October 2020) of THC-containing CBM use in people age 50 years and older to determine any associations with neuropsychiatric effects. The authors identified 30 randomized, controlled trials (RCTs) using THC-only CBMs and 24 RCTs using CBD and THC combinations. There were 1,417 patients in intervention groups and 1,210 patients in control groups for the THC-only RCTs. There were 1,917 patients in intervention groups and 1,835 patients in control groups for the CBD and THC combination RCTs. In the THC-only studies, higher THC doses were significantly associated with an increase in dizziness or lightheadedness (incident rate ratio estimate, 0.05; 95% CI, 0.02-0.08; P = 0.001) and an increase in thinking or perception disorder (incident rate ratio estimate, 0.07; 95% CI, 0.03-0.11; P < 0.001). There was no evidence of association with higher THC doses and other neuropsychiatric effects for either the THC-only or CBD and THC combination RCTs.

The authors concluded that in older adults, higher THC doses resulted in a more frequent occurrence of dizziness or lightheadedness and thinking or perception disorder. Additionally, THC use did not appear to increase the risk of other neuropsychiatric effects in this population.

COMMENTARY

These findings demonstrate the need for physicians and their patients to be aware of potential adverse effects of THC-containing CBMs. As is the case for many medications, adverse effects of CBMs in the older population may be different than for younger populations. Dizziness and lightheadedness can be especially dangerous for older adults because of a higher risk of falls and delirium, which often lead to poor outcomes, such as placement in long-term care facilities and death. Thus, THC-containing CBMs should be used with caution in patients age 50 years and older, and patients should be educated correctly on the potential risks and benefits of these treatments. Although Velayudhan et al employed sound methodology for identifying THC-containing CBM RCTs, the overall results are limited by individual study quality of the RCTs, each of which received very low to moderate Grading of Recommendations, Assessment, Development, and Evaluations scores. Many trial authors did not employ structured questionnaires to identify adverse effects, relying instead on patient self-reporting, possibly resulting in underreporting of neuropsychiatric effects. Notably, the authors reflected that a primary limitation of the research is few studies included patients age 65 years and older (n = 4), rendering a sensitivity analysis in this subgroup impractical. Since many of the conditions for which CBMs are studied involve this population, more evidence is needed to draw conclusions about adverse effects and correctly advise patients age 65 years and older of the risks and benefits of CBMs.

REFERENCES

  1. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015;313:2456-2473.
  2. Bhattacharyya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 2010;35:764-774.
  3. Levy C, Galenbeck E, Magid K. Cannabis for symptom management in older adults. Med Clin North Am 2020;104:471-489.
  4. Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): A multicentre case-control study. Lancet Psychiatry 2019;6:427-436.