Neurotherapeutics (2015) 12:788–792

DOI 10.1007/s13311-015-0376-4

REVIEW

Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics

Published online: 14 August 2015

Abstract Cannabis has been used for many medicinal pur- Keywords Cannabis . Marijuana . THC . Cannabidiol .
poses, including management of spasms, dystonia, and dyski- Dystonia . Dyskinesias . Chorea . Tics
nesias, with variable success. Its use for tetanus was described
in the second century BCE, but the literature continues to
include more case reports and surveys of its beneficial effects Introduction
in managing symptoms of hyperkinetic movement disorders
than randomized controlled trials, making evidence-based rec- Endocannabinoid receptors (CB1R and CB2R) are plentiful in
ommendations difficult. This paper reviews clinical research the basal ganglia [1], implying they play a role in normal
using various formulations of cannabis (botanical products, motor function and that pharmaceutical (or recreational) can-
oral preparations containing Δ9-tetrahydrocannabinol and/or nabis formulations, which are agonists at both sites, might
cannabidiol) and currently available preparations in the USA alleviate symptoms of movement disorders. CB 1 R are
(nabilone and dronabinol). This has been expanded from a expressed in γ-aminobutyric acid (GABA)ergic neurons of
recent systematic review of cannabis use in several neurologic the caudate and striatum, presynaptic terminals in the globus
conditions to include case reports and case series and results of pallidus externa and interna, substantia nigra pars reticulate
anonymous surveys of patients using cannabis outside of and pars compacta, and are present in glutamatergic projec-
medical settings, with the original evidence classifications tions to and from the cortex and the subthalamic nucleus. In
marked for those papers that followed research protocols. De- addition to GABAergic and glutamatergic pathways, dopami-
spite overlap in some patients, dyskinesias will be treated sep- nergic inputs are also influenced by endocannabinoids. In
arately from dystonia and chorea; benefit was not established general, the cannabinoid signals would be upregulated if a
beyond individual patients for these conditions. Tics, usually disease was marked by hypokinesis, such as in Parkinson
due to Tourettes, did respond to cannabis preparations. Side disease (PD), as the cannabinoid ligands act overall to sup-
effects reported in the trials will be reviewed but those due to press movement, and would be decreased in hyperkinetic
recreational use, including the dystonia that can be secondary movement disorders such as Huntington disease (HD). How-
to synthetic marijuana preparations, are outside the scope of ever, paradoxical responses can occur during degeneration as
this paper. the receptors in various parts of the basal ganglia die (Table 1).
The complexity of feedback loops in this region, with in-
direct actions of the endocannabinoid system modulating oth-
er inhibitory, excitatory or dopaminergic transmission, partial-
ly explains this. In addition, in degenerative diseases such as
HD and PD, progressive loss of specific structures, along with
* Barbara S. Koppel their endocannabinoid receptors occurs. The receptor loss will
[email protected] dampen any effects of CB1/2R agonists such as Δ9-tetrahy-
drocannabinol (THC) and cannabidiol (CBD). Other
1
New York Medical College, Metropolitan Hospital, 1901 First Ave. endocannabinoid receptors, such as transient receptor poten-
Suite 7C5, New York, NY 10029, USA tial vannilloid-type 1, may be successfully stimulated in early
Cannabis use in movement disorders 789

Table 1 Cannabis formulations used in various movement disorders

Generic name Trade name Use Dosage and component(s) Reference

PD
Cannabis extract Cannador Dopa-induced dyskinesias/dystonia Δ9-THC 2.5 + CBD 1.25 [7, 10* 16, 17*, 18*]
Not stated Tremor/dystonia 100–600 mg/daily
dopa-induced dyskinesias 0.03 mg/kg/daily
25mgTHC/kg//daily
75 mg/daily
Rimonabant (CBD antagonist) SR141716 Dopa-induced dyskinesias Experimental [20]
Inhaled botanical marijuana – Parkinson tremor and dyskinesias 1 cigarette 2.9 % THC [13*,14, 15, 19]
Survey of unsupervised
smoked marijuana 0.5gm/cig
Nabilone Cesamet Levodopa-induced dyskinesias Synthetic cannabinoid [10*, 16]
0.03 mg/kg
0.03 mg/kg
Dystonia
Dronabinol Marinol Cervical dystonia 7.5 mg twice daily [5*, 11]
Dystonia and tics in MS 2.5 mg twice daily
CBD or cannabis extract None Primary dystonias 10 mg/kg/day up to 75 mg/day [7, 18*, 23]
100 mg CBD
Inhaled botanical marijuana Spasms Not stated [6, 8, 9]
Hemidystonia (in Wilson disease) 1 MJ Cigarette/dy
3–4 g/day
HD
Nabilone Cesamet Motor score no improvement, 1–2 mg/day [23*†, 24*]
some in chorea and NPI
CBD or cannabis extract None 10 mg/kg/day, mean 700 mg [21*‡]
Tourette syndrome
Botanical smoked marijuana 0.5–2.0 cigarettes/day [25–27]
One Bcone^/night survey
(self-prescribed)
THC capsule None Tics and vocalizations 2.5 mg Δ9-THC, maximum 10 mg/day [28†, 29 ‡]

If no evidence classification is indicated, it means it was class IV. PD = Parkinson disease; Δ9 -THC = Δ9 -tetrahydrocannabinol (the principal
psychoactive agent); CBD = cannabidiol (a lesspsychoactive resin extract constituent of the plant Cannabis Sativa); MS = multiple sclerosis; HD =
Huntington disease; NPI = Neuropsychiatric index
*Class I
†
Class II
‡
Class III

stages of HD, but medications do not exist yet to test this. In efficacy. The potency, especially Δ9-THC content, is kept de-
fact, CB1R antagonists, similarly experimental at this stage, liberately low to limit side effects (or patient recognition in
might be beneficial for hypokinetic symptoms such as those experienced with marijuana), which contributes to treat-
hypokinesia in PD. ment failure. Studies are small with problematic recruitment
Contradictory and confusing efficacy has been reported for a substance that will require limitation of activities such as
when cannabis medications (or smoked phytocannabinoids) driving, use of a stigmatized medication, and of short duration
are used to treat movement disorder symptoms [2, 3]. Al- (sometimes single dose) to avoid abuse or addiction [4]. Even
though the loss of receptors plays some role, more likely cur- obtaining study drug status in the USA requires working with
rently available cannabis preparations, which contain different the various government agencies, and is only becoming easier
amounts and combinations of cannabinoids (at least 60 have in the face of a serious epidemic of opiate overuse and toxicity.
been described) with variable potency and psychoactive con- The Drug Enforcement Agency continues to classify medical
tent (present in Δ9-THC but not CBD) with different, usually cannabis as a Schedule I drug (that with no therapeutic use).
low, doses, make standardized comparisons impossible. Scor- Investigation into cannabis’ medicinal use began with
ing methods, other than counting individual tics or choreiform promising case reports and anonymous surveys, followed by
movements, add to the researcher’s difficulty in measuring limited clinical research often conducted outside the USA,
790 Koppel

which has not proved sufficient to allow many evidence-based tone and motor function through the effect of the endogenous
recommendations. Although overlap exists in individuals, in cannabinoid ligand, arachidonylethanolamide (anadamide),
this review dyskinesias, dystonia, and chorea will be consid- on modulation of GABA transmission [12]. Many studies
ered separately. Although tremor was studied in patients suf- have been done with primate or rat models to determine if
fering from multiple sclerosis, there is no information on es- cannabinoid agonists or antagonists could act to suppress dys-
sential tremor. Tics will be considered separately, as the mech- kinesias without exacerbating hypokinesis; however, transla-
anism differs. tion to patients has proved difficult.
Since the initial observation in 1991 of no improvement of
resting tremor in 5 patients who smoked one marijuana ciga-
Dystonia rette [13], surveys have been done asking patients with PD to
say if they had tried marijuana on their own (presumably the
Dystonia involves overactivity of muscles required for normal smoked botanical form) and if so with what effect. Venderova
movement, with extra force or activation of nearby but unnec- sent surveys to 630 patients attending a movement disorders
essary muscles, including those that should be turned off to clinic in Prague, and of the 339 respondents, 25 % had used
facilitate movement, and is often painful in addition to inter- marijuana. Of these 85 patients, 39 benefitted in rest tremor
fering with function. It can be primary, as in torticollis and (31 %), bradykinesia (45 %), and dyskinesias (14 %), and
blepharospasm/orofacial dyskinesias or dystonias (Meige syn- continued its daily use [14]. A recent survey of Colorado
drome) or as part of another condition such as HD and tardive residents with Parkinson using all types of complementary
dyskinesia after dopa-blocking drugs. The globus pallidus and therapies found 9 using medical marijuana (4 %), reporting
substantia nigra pars reticularis contain CB1R, with cannabi- improvement of mood and sleep, but only 2 with improve-
noids acting as neuromodulators and enhancing GABA re- ment of motor symptoms, not specifically dyskinesias [15].
lease and reducing its reuptake [5]. A small but class III randomized double-blind study using
In 1981, Marsden described improvement in a patient with nabilone (synthetic Δ9-THC) showed a significant reduction
torticollis who smoked cannabis [6]. An open-label series in Rush score on levodopa-induced dyskinesias in 7 patients,
followed [7], and self-reported improvement with smoking observed and measured with the Rush dyskinesia scale [16],
marijuana was described in 2002 in a patient with central pain and 2 reported improvement in dystonia occurring in the off
and dystonia and in a patient with Wilson disease [8, 9]. period for dopa. In a study of 17 patients using the oral prep-
Cannabidiol showed improvement of 20–50 % by videotape aration Cannador (2.5 mg Δ9-THC/1.25 mg CBD) no im-
review in 5 patients [9], but higher doses exacerbated tremor provement was noted in dyskinesias as measured in Q32–34
and hypokinesis in 2 patients with PD and levodopa-induced of the Unified Parkinson’s disease rating scale scale (the pri-
dystonia. Nabilone, a synthetic oral form of Δ9-THC, which is mary outcome), or other scales including Parkinson Disease
available in the USA for other indications, was not found to be Questionnaire-39 scale, nor was there a dose response [17].
effective in 1 administration of escalating doses of 0.03 mg/kg The study by Carrol et al. [17] was the only one considered
using a dystonia rating scale; however, 3/15 patients felt better class I for the purposes of evidence-based recommendations.
for several days after its use [10]. Another currently available Various doses of cannabidiol were given to 21 patients over
oral form of Δ9-THC, dronabinol, did not improve symptoms 6 weeks; no change was found in the total motor score, despite
of cervical dystonia, as demonstrated by the Toronto Western improvement in the quality of life section of the Unified
Hospital Spasmodic Torticollis Rating Scale in a 3-week treat- Parkinson’s disease rating scale if the target dose of 300 mg
ment trial [5]. Finally, response to dronabinol 2.5 mg twice daily was reached, which was possible in only 35 % of the
daily in a case report of dystonia (and tics) in a patient with patients [18]. Finally, an open-Blabel^ study of smoked mari-
multiple sclerosis who had previously reported symptom im- juana in 22 Israeli patients showed improvement in the num-
provement after smoking marijuana [11]. ber of dyskinesias observed after dopa challenge, 30 min after
Side effects described in these studies included hypoten- smoking the cigarette [19]. In an interesting twist, a single
sion and sedation at higher doses of nabilone [10], insomnia dose of the CB1R antagonist rimonabant (SR141716) was
and tachycardia from dronabinol [5], and hypokinesia and found to have no effect on motor symptoms, or induced dys-
tremor of PD [10]. kinesias in 8 patients [20].
Side effects mentioned in the studies included hypotension,
vertigo, hyperacusis, and disorientation and visual hallucina-
Dyskinesias from Levodopa (in Advanced PD) tions [15], somnolence, dizziness and bad taste, with hypogly-
cemia in 1 patient [19], and, rarely, bradykinesia, but in the
The plethora of endocannabinoid receptors in the basal gan- few studies where it was measured [17], there was no effect on
glia, especially the globus pallidus interna, pars reticulata, and cognitive function as measured by Mini Mental State Exami-
cerebellum indicate they must be playing a role in regulating nation; in fact, an improvement in Mini Mental State
Cannabis use in movement disorders 791

Examination was noted, which was attributed to a practice Tourette Syndrome Tics
effect but may have been precognitive (the 4-week trial was
too short to call cannabis neuroprotective). As in any condition influenced by anxiety, a nonspecific ben-
In summary in PD, the symptom that responded best to eficial effect of cannabis might be expected, but given the
cannabis, levodopa-induced dyskinesias, is a fairly rare com- presence of endocannibinoid receptors in the striatum, it is
plication of dopamine replacement in advanced cases. The possible that a direct effect of cannabis is reducing the number
role of cannabis in other symptoms of PD is unclear, and these of tics.
symptoms vary according to the stage of neurodegeneration Success in treating symptoms of Tourette sydrome,
and also to the state of treatment with dopamine transmitter including involuntary movements (tics) and compulsive
replacement. As there is the potential of cannabis worsening behaviors, was first mentioned in an observation of 3
some symptoms, especially hypokinesia, very careful research patients who, in 1988, noted improvement in tics and
must be done with PD. urges while smoking marijuana cigarettes [25], followed
by another case of a patient remaining symptom free for
a year while smoking marijuana daily [26]. In 1998 a
Dyskinesias in HD survey of a larger population confirmed a reduction in
tic or complete remission in 82 % of patients [27]. The
Abnormalities of motor function, along with psychiatric and same authors used Δ 9 -THC capsules of varying
cognitive dysfunction, are a main feature of HD, a dominantly strengths in a single dose in 12 patients (class II study)
inherited neurodegenerative disease. Cannabis products have and reported improvement in scores of the Tourette
been most often used to ameliorate agitation and other psychi- Syndrome Symptom List and obsessive–compulsive be-
atric symptoms, but the presence of endocannibinoid recep- havior scores, with a decreased number of complex mo-
tors in the striatum, where they modulate GABA transmission tor tics observed by the examiner [28]. The following
and affect glutamate release, suggests a role for management year, in a study of 24 patients using the maximum-
of the excessive involuntary movements (choreoathetosis or strength Δ9-THC capsule from the pilot study (10 mg)
dystonia) of HD. As in other degenerative processes, these for 6 weeks, a significant response in self-rated Tourette
receptors can decrease as the disease progresses, leaving less score and observer-rated scores, including the Tourette
response to cannabinoid agonists as the brain’s substrate Syndrome Clinical Global Impression Scale, the Shapiro
changes. Obviously, current or prior use of dopamine- Tourette Syndrome Severity Scale, and the Yal Global
blocking medication (neuroleptics), which can superimpose Tic Severity Scale, as well as the review of video, was
tardive dyskinesias on the direct movements of HD, will also noted [29]. These were then summarized in a Cochrane
change the therapeutic effects of cannabis. review [30]. Little additional work was summarized in a
Consroe et al. [21] first reported the clinical use of CBD in more recent review [31]. Of note, improvements oc-
HD in 1991. This class III study of 15 patients receiving can- curred without exacerbating performance on
nabis extract in capsule form (10 mg/kg), crossing to placebo neuropsychologic testing [32].
over a 15-week period, off neuroleptics for at least 2 weeks, Side effects were minimized by a simple technique of pro-
found no difference in the chorea severity score of Marsden viding dronabinol after breakfast in order to slow its absorp-
and Quinn, or on videotape and live assessment of chorea tion and provide a steady level acting in the brain [29].
severity, nor on secondary end points of Shoulson and Fahn
disability scores, finger tapping, or manipulation. Side effects,
as checked off a symptom inventory, did not vary between Conclusions
placebo and treated patients. After a case report in a patient
who had improved mood and movements after smoking mar- Although clinical studies in this area are difficult to do,
ijuana and then taking prescribed nabilone, 1 mg daily [22], even in countries where the use of cannabis has been
the authors gave 1 or 2 mg of nabilone to 37 patients in a class allowed for years, there is a clear role for cannabis prod-
II study [23]. Despite improvement in the secondary measures ucts in symptom management for these difficult condi-
of neuropsychiatric index and chorea score, the primary out- tions. The movement disorders are well-known to be
come, total motor score of the Unified Huntingdon Disease worsened in patients who are anxious, but the careful
Rating Scale, showed only a modest response, with no dose observations reviewed above lead to the conclusion that
response (i.e., 2 mg was not better than 1 mg). there is a direct effect of cannabis in various formula-
Drowsiness and forgetfulness were the main reported ad- tions in some conditions, especially hyperkinetic symp-
verse events in both groups, with no increase in psychosis or toms. Caution in using a potential central nervous system
euphoria in the treated group. In 1 case nabilone actually depressant is always required in patients whose neuro-
caused increased chorea [24]. logic function is already compromised by disease, but
792 Koppel

larger studies will prove there is a promising role for this Parkinson’s disease patients in Colorado. Evid Based
Complement Alternat Med 2015;2015:874849.
class of drug in the therapy of dyskinesias, tics, and
16. Sieradzan KA, Fox SH, Hill M, et al. Cannabinoids reduce
possibly dystonia. levodopa-induced dyskinesia in Parkinson’s disease: a pilot study.
Neurology 2001;57:2108-2111.
17. Carroll CB, Bain PG, Teare L, et al. Cannabis for dyskinesia in
Required Author Forms Disclosure forms provided by the authors are Parkinson disease: a randomized double-blind crossover study.
available with the online version of this article. Neurology 2004;63:1245-1250.
18. Chagas MH, Zuardi AW, Tumas V, et al. Effects of cannabidiol in
the treatment of patients with Parkinson’s disease: an exploratory
double-blind trial. J Psychopharmacol 2014;28:1088-1098.
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