Treatment of Tourette's Syndrome with Δ⁹-Tetrahydrocannabinol (THC): A Randomized Crossover Trial

Abstract

Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results.

Treatment of Tourette Syndrome with Delta-9-Tetrahydrocannabinol (Δ9-THC): No Influence on Neuropsychological Performance

“…Clinical trials provide evidence that D 9 -THC is effective in the treatment of motor and vocal tics and associated behavioral problems such as obsessive-compulsive behavior in TS (Müller-Vahl, 2001;Müller-Vahl et al, 2002). Previous studies in healthy marijuana users, however, suggested that cannabinoids may cause acute and/or longterm effects on cognition (Kleiber and Kovar, 1998).…”

“…Anecdotal reports (Sandyk and Awerbuch, 1988;Hemming and Yellowlees, 1993;Müller-Vahl et al, 1998 and two controlled studies (Müller-Vahl, 2001;Müller-Vahl et al, 2002) provide evidence that marijuana (Cannabis sativa) and delta-9-tetrahydrocannabinol (D 9 -THC), the major psychoactive ingredient of marijuana, respectively, are effective in the treatment of tics and behavioral problems in TS.…”

“…No significant differences could be observed 4 weeks after use, suggesting that cannabis-induced cognitive deficits were reversible and not related to cumulative lifetime use. Since previous studies in TS (Müller-Vahl, 2001, Müller-Vahl et al, 2002 have demonstrated a significant reduction of tics after treatment with D 9 -THC, it can be speculated that the central CB1 receptor system might be involved in the pathology of the disease. The endogenous CB1 receptor system is thought to play a role in both motor control and memory, emotion, and other cognitive functions (Hall and Solowij, 1998).…”

Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics

“…In 1998 a survey of a larger population confirmed a reduction in tic or complete remission in 82 % of patients [27]. The same authors used Δ 9 -THC capsules of varying strengths in a single dose in 12 patients (class II study) and reported improvement in scores of the Tourette Syndrome Symptom List and obsessive-compulsive behavior scores, with a decreased number of complex motor tics observed by the examiner [28]. The following year, in a study of 24 patients using the maximumstrength Δ 9 -THC capsule from the pilot study (10 mg) for 6 weeks, a significant response in self-rated Tourette score and observer-rated scores, including the Tourette Syndrome Clinical Global Impression Scale, the Shapiro Tourette Syndrome Severity Scale, and the Yal Global Tic Severity Scale, as well as the review of video, was noted [29].…”

Efficient synthesis of functionalized spiro[imidazolidine-2-thione-oxindoles] via catalyst-free domino Mannich cyclization

“…The spirocyclic oxindole derivatives are recognized as attractive synthetic targets because of their prevalence in numerous natural products and pharmaceutical agents as well as useful intermediates for the easy access of a variety of heterocyclic compounds by rearrangement reaction due to their steric strain associated with the quaternary carbon. [1][2][3][4] Recently, 3-isothiocyanato oxindoles have been used as the most attractive substrates in catalytic cascade Michael/cyclization reactions, [5][6][7][8][9] Mannich/cyclization reactions [10][11] Aldol/cyclization reactions [12][13] and [3+2] cyclization [14][15][16][17][18] for the synthesis of the highly functionalized spirocyclic oxindole derivatives.…”