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:
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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 tourettes
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