Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Δ9-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 Δ9-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-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ9-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 Δ9-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 Δ9-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.
References
-
1
Cocchetto D M, Owens S M, Perez-Reyes M, DiGuiseppi S, Miller L L.
Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man.
Psychopharmacology (Berl).
1981;
75
158-164
-
2
Glass M, Brotchie J M, Maneuf Y P.
Modulation of neurotransmission by cannabinoids in the basal ganglia.
Eur J Neurosci.
1997;
9
199-203
-
3
Harcherik D F, Leckman J F, Detlor J, Cohen D J.
A new instrument for clinical studies of Tourette's syndrome.
Am J Acad Child Psychiatry.
1984;
23
53-160
-
4 Harvey D J. Metabolism and pharmacokinetics of the cannabinoids. In Watson RR, editor Biochemistry and physiology of substance abuse. Boca Raton, Ann Arbor, Boston: CRC Press 1991 III: 279-365
-
5
Hemming M, Yellowlees P M.
Effective treatment of Tourette's syndrome with marijuana.
J Psychopharmacol.
1993;
7
389-391
-
6
Herkenham M, Lynn A B, Little M D, Johnson M R, Melvin L S, de Costa B R, Rice K C.
Cannabinoid receptor localization in brain.
Proc Natl Acad Sci USA.
1990;
87
1932-1936
-
7
Hill M, Armitage P.
The two period cross-over clinical trial.
Br J Clin Pharmacol.
1979;
8
7-20
-
8
Hollister L E.
Cannabis - 1988.
Acta Psychiatr Scand.
1988;
345
108-118
-
9 Korczyn A D. Future therapies. In Kurlan R, editor Handbooks of Tourette's syndrome and related tic and behavioral disorders. New York, Basel, Hong Kong: Marcel Dekker, Inc 1993: 481-490
-
10
Kurlan R, Majumdar L, Deeley C, Mudholkar G S, Plumb S, Como P G.
A controlled trial of propoxyphene and naltrexone in patients with Tourette's syndrome.
Ann Neurol.
1991;
30
19-23
-
11 Kurlan R, McDermott M P. Rating tic severity. In Kurlan R, editor Handbook of Tourette's syndrome and related tic and behavioral disorders. New York, Basel, Hong Kong: Marcel Dekker, Inc 1993: 199-220
-
12 Leckman J F, Towbin K E, Ort S I, Cohen D J. Clinical assessment of tic disorder severity. In Cohen DJ, Bruun RD, Leckman JF, editors Tourette's syndrome and tic disorders. New York: John Wiley 1988: 55-78
-
13
Lemberger L, Crabtree R E, Rowe H M.
11-hydroxy-9-tetrahydrocannabinol: pharmacology, disposition, and metabolism of a major metabolite of marihuana in man.
Science.
1972;
177
62-64
-
14
Lemberger L, Weiss J L, Watanabe A M, Galanter I M, Wyatt R J, Cardon P V.
Delta-9-tetrahydrocannabinol. Temporal correlation of the psychologic effects and blood levels after various routes of administration.
N Engl J Med.
1972;
286
685-688
-
15
Mailleux P, Vanderhaeghen J -J.
Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons.
Neurosci Lett.
1992;
148
173-176
-
16
Mason A P, McBay A J.
Cannabis: Pharmacology and interpretation of effects.
J Forensic Sci.
1985;
30
615-631
-
17
McBay A J.
Drug concentration and traffic safety.
Alcohol Drugs Driving..
1986;
2
51-59
-
18
Müller-Vahl K R, Kolbe H, Dengler R.
Gilles de la Tourette-Syndrom - Eine aktuelle Übersicht.
Akt Neurol.
1997;
24
12-19
-
19
Müller-Vahl K R, Kolbe H, Schneider U, Emrich H M.
Cannabinoids: Possible role in pathophysiology of Gilles de la Tourette's syndrome.
Acta Psychiat Scand.
1998;
98
502-506
-
20
Müller-Vahl K R, Schneider U, Kolbe H, Emrich H M.
Treatment of Tourette's syndrome with delta-9-Tetrahydrocannabinol.
Am J Psychiatry.
1999;
156
495
-
21
Ohlsson A, Lindgren J E, Wahlen A, Agurell S, Hollister L E, Gillespie H K.
Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking.
Clin Pharmacol Ther.
1980;
28
409-416
-
22
Robertson M M, Stern J S.
Tic disorders: new developments in Tourette's syndrome and related disorders.
Current Opinion Neurol.
1998;
11
373-380
-
23
Rodriguez de Fonseca F, Del Arco I, Martin-Calderon J L, Gorriti M A, Navarro M.
Role of the endogenous cannabinoid system in the regulation of motor activity.
Neurobiol Dis.
1998;
5
483-501
-
24
Sandyk R, Awerbuch G.
Marijuana and Tourette's Syndrome.
J Clin Psychopharmacol.
1988;
8
444-445
-
25
Schou J, Prockop L D, Dahlstrom G, Rohde C.
Penetration of delta-9-tetrahydrocannabinol and 11-OH-delta-9-tetrahydrocannabinol through the blood-brain barrier.
Acta Pharmacol Toxicol (Copenh).
1977;
41
33-38
-
26 Shapiro A K, Shapiro E S, Young J G, Feinberg T E. Signs, symptoms, and clinical course. In Shapiro AK, Shapiro ES, Young JG, Feinberg TE, editors Gilles de la Tourette's syndrome. New York: Raven Press 1988 2: 127-193
-
27
Wall M E, Perez-Reyes M.
The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man.
J Clin Pharmacol.
1981;
21
(8-9)
178S-189S
-
28
Wall M E, Sadler B M, Brine D, Taylor H, Perez-Reyes M.
Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women.
Clin Pharmacol Ther.
1983;
34
352-363
Dr. Kirsten R. Müller-Vahl
Department of Clinical Psychiatry and Psychotherapy
Medical School Hannover
Carl-Neuberg-Str. 1
30625 Hannover
Germany
Email: mueller-vahl.kirsten@mh-hannover.de
