Skip to main content
Udow and co authors [1] discuss the skilful management of an elderly patient with Parkinson’s disease and good cognitive status who developed acute and persistent psychosis after exposure to nabilone. The patient eventually recovered, although not to baseline.
Phytocannabinoids such as tetrahydrocannabivarin THCV and Cannabidiol have been recommended as disease modifying agents in Parkinson’s disease. Both agents were neuroprotective in 6-hydroxy dopamine lesioned rats, independent of cannabinoid receptor activity, likely due to anti-oxidant properties [2]. Although CB1 receptor agonism may also have disease modifying potential, motor effects generally arise as a consequence of changes in endocannabinoid system with activation of the CB1 receptor and inhibition of movement.
The referring physician’s decision to prescribe a synthetic cannabinoid with unopposed CB1 receptor agonism for this patient’s symptoms is not aligned with such considerations. The authors are not correct to state: “Nabilone is a mixture of cannabinoids, primarily cannabinol but it also contains THC and cannabidiol”. Instead, nabilone is a pure white crystalline powder with the chemical name (±)-trans-3-(1,1-dimethylheptyl)-6,6a,7,8,10,10a-hexahydro-1-hydroxy6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one [3].
The dramatic and persistent CB1 mediated psychosis in association with nabilone can be attributed to the unique pharmacology of nabilone. This agent is a partial CB1 and CB2 agonist with a narrow therapeutic index. Side effects of dry mouth, dizziness, drowsiness, postural hypotension and tachycardia are highly prevalent in cannabis naïve patients treated with synthetic cannabinoids [4, 5]. The initially prescribed dose of 1 mg is 4 times greater than the smallest dose formulation of 0.25 mg. Cannabidiol enriched (CBD) medical cannabis products (typically 0.5-2 mg / ml of THC and 15-20 mg / ml of CBD) are preferred in practice for disease modification owing to the anti-psychotic effects of cannabidiol [6, 7].
Rational prescribing for disease modification in an unwell elderly woman would have emphasized a cannabidiol enriched product, and the complete avoidance of a potent synthetic CB1 agonist.
1. Udow SJ, Freitas ME, Fox SH, Lang AE. Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old woman with Parkinson disease. CMAJ. 2018;190:E50-E52.
2. García C, Palomo‐Garo C, García‐Arencibia M, Ramos JA, Pertwee RG, Fernández‐Ruiz J. Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson’s disease. Br J Pharmacol. 2011;163(7):1495-1506.
3. Nabilone [product monograph]. Toronto, ON. Teva Canada Limited, submission control no. 139940. 2012.
4. Jain AK, Ryan JR, McMahon FG, Smith G. Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J Clin Pharmacol. 1981;21(8-9 Suppl):320S-326S.
5. Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain. 2003;106(1-2):169-172.
6. Mechoulam R, Parker LA, Gallily R. Cannabidiol: An overview of some pharmacological aspects. J Clin Pharmacol. 2002;42(11 Suppl):11S-19S.
7. Russo Ethan B. Taming THC: Potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.