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MARIJUANA AND TOURETTE'S SYNDROME

Journal of Clinical Psychopharmacology, Vol. 8/No. 6, Dec 1988

Editors:

Although a variety of pharmacological agents have been reported to

attenuate symptoms of Tourette's syndrome (TS), the pathophysiology of this

disorder remains unknown. Apart from the presence of disabling motor and

vocal tics, TS patients often experience behavioral disturbances including

obsessive compulsive thoughts, anxiety, depression, abnormal sleep

disturbances. (1) Drug abuse to obtain relief from the chronic anxiety may

be common among these patients. (2) (3) We recently encountered three

patients with TS who experienced incomplete responses to conventional

anti-TS drugs but noted a significant amelioration of symptoms when smoking

marijuana.

The first patient was a 15-year-old boy who, in addition to motor

tics, had obsessive compulsive and self-mutilatory behavior improved with

administration of imipramine (37.5 mg/day) combined with the oral opiate

receptor antagonist naltrexone (dose range 50 to 100 mg/day). During

recreational use of marijuana (1 to 2 cigarettes/day), he noted general

relaxation and marked lessening in his urge to tic. According to the

patient's mother, motor tics had decreased by about 50% and there was also

some reduction in the frequency of the self-mutilatory behavior. The

patients had been smoking marijuana for 4 weeks, and upon discontinuation,

noted rebound exacerbation of symptoms within 12 hours.

The second patient, age 17, had had severe motor tics since the age

of 7 years. He had frequent jerk-type movements of his neck muscles

associate with infrequent vocalizations during stressful situations. His

management had been difficult as he was unable to tolerate haloperidol or

clonidine. Administration of naltrexone (150 mg/day) reduced his anxiety

level and the urge to tic; this was the only drug he could tolerate. On

several occasions, he had smoked marijuana and noted generalized relaxation

accompanied by reduction in the severity of the motor tics and improvement

in attention span. He volunteered that smoking one cigarette reduced the

frequency of his motor tics by about 60% to 70%, which was sustained over

several hours.

The third patient was a 39-year-old man who had had symptoms of TS

since the age of 9 years. His symptoms included frequent jerking-type

movements of his neck and upper extremity muscles, facial grimacing,

frequent blinking, and leg jerking. Vocalizations were not noted except

during extreme anxiety. In addition he was troubled by chronic insomnia

and hypersexuality. He reported no benefit from haloperidol, clonidine, or

benzodiazepines but experienced some relief after consuming large amounts

of ethanol. He also admitted that marijuana smoking (1/2 to 1

cigarette/day) produced relaxation with subsequent reduction in the

severity of the motor tics along with marked attenuation of his

hypersexuality.

From 1842 to the turn of this century, several reports in the

literature have indicated that marijuana smoking was used extensively as an

analgesic, sedative, and hypnotic agent. (4) Moreover, oral cannabis

preparations were useful in the management of diverse neurological

conditions including convulsions and chorea. (5) Much more recently it was

reported anecdotally that patients with dystonia improved with their

alleged cannabis smoking. (6) The cannabis constituent cannabidiol was

reported efficacious in reducing symptoms of dystonia. (7,8) and

Huntington's chorea. (9) In experimental animals, cannabidiol has been

shown to exert anticonvulsant and antianxiety properties and affect

apomorphine-induced turning behavior in rats. (10) The latter report

suggested that cannabidiol exerts antidyskinetic effects through modulation

of striatal dopaminergic activity. Tetrahudrocannabinol (THC, the active

compound of marijuana) may exert GABA-ergic as well as antiserotonergic

effects. (11) A recent report has demonstrated that THC reduces opiate

receptor binding sites and modulates opiod receptors in a noncompetitive

manner. (12) THC may also exert effects on the cholinergic system. (13)

Considering evidence that marijuana may exert effects on a large

number of neurotransmitters, it is difficult to speculate on its mode of

action in attenuating symptoms of TS. It is reasonable to assume that the

effects of marijuana in TS may be largely related to its anxiety-reducing

properties, although a more specific antidyskinetic effect cannot be

excluded. Should marijuana compounds prove to have specific actions in TS,

chemical modifications which eliminate the psychoactive properties while

retaining the antiduskinetic effects (e.g., cannabidiol) could promise a

new class of drugs useful in the management of TS. Further studies are

clearly needed in both the clinical and basic laboratory realms to further

characterize the effects of cannabinoids in TS.

Reuven Sandyk, MD, MSc

Gavin Awerbuch, MD

University of Arizona

Tucson, Arizona

References

1. Brunn RD. Gilles de la Tourette Syndrome: an overview of clinical

experience. J Am Acad Child Psychiatry 1984;23: 125-33.

2. Mesulam MM. Cocaine and Tourette's syndrome. N Engl J Med 1986; 315:

398.

3. Sandyk R, Gillman MD. Gilles de la Tourette syndrome following

alcohol withdrawal. Br J Addict 1985; 80: 213-4.

4. Consroe P, Snider SR. Therapeutic potential of cannabinoids in

neurological disorders. In: Mechoulam R, ed. Cannabinoids as therapeutic

agents. Boca Raton, FL: CRC Press, 1986: 21-49.

5. O'Shaughnessy R. On the preparation of the indian hemp or gunjah

(cannabis indica): the effects on the animal system in health and their

utility in the treatment of tetanus and other convulsive diseases. Trans

Med Phys Soc Bombay 1842; 8: 421-61.

6. Marsden CD. Treatment of torsion dystonia. In: Barbeau A, ed.

Disorders of movement, current status of modern therapy, Vol. 8.

Philadelphia: Lippincott, 1981: 81-104.

7. Snider SF, Consroe P. Treatment of Meige's syndrome with cannabidiol.

Neurology 1984; 34 (Suppl): 147.

8. Consroe P, Sandyk R, Snider SR. Open label evaluation of cannabidiol

in dystonic movement disorder. Int J Neurosci 1986; 30: 277-80.

9. Sandyk R, Consroe P, Stern LZ, Snider SR. Effects of cannabidiol in

Hungtington's disease. Neurology 1986; 36 (suppl): 342.

10. Conti LH, Johannesen J, Musty RE, Consroe P. Anti-dyskinetic effects

of cannabidiol. Proceedings of the International Congress on Marijuana.

Melbourne, Australia: Melbourne University Press 1987: 21.

11. Revuelta AV, Cheney DL, Wood PL, Costa E. Gabergic mediation in the

inhibition of hippocampal acetylcholine turnover rate elicited by

delta-9-tetrahudrocannabidiol. J Clin Pharmacol 1979; 18: 525-30.

12. Vaysse PJJ, Gardner EL, Zukin RS. Modulation of rat brain opiod

receptors by cannabinoids. J Pharmacol Exp Ther 1987; 241: 534-9.

13. Revuelta AV, Moroni F, Cheney DL, Costa E. Effect of cannabinoids on

the turnover rate of acetylcholine in rat hippocampus, striatum and cortex.

Naunyn Schmiedebergs Arch Pharmacol 1978; 304: 107-11.

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