Meinck/MS/1989

EFFECT OF CANNABINOIDS ON SPASTICITY AND ATAXIA IN MULTIPLE SCLEROSIS*

H.M. Meinck, P.W. Schonle, and B. Conrad

Department of Clinical Neurophysiology, University of Gottingen, Federal
Republic of Germany

J Neurol (1989) 236: 120-122

Summary. The chronic motor handicaps of a 30-year-old multiple sclerosis
patient acutely improved while he smoked a marihuana cigarette. This
effect was quantitatively assessed by means of clinical rating,
electromyographic investigation of the leg flexor reflexes and
electromagnetic recording of the hand action tremor. It is concluded that
cannabinoids may have powerful beneficial effects on both spasticity and
ataxia that warrant further evaluation.

Key words: Multiple
sclerosis---Spasticity---Ataxia---Cannabinoids---Flexor reflex

Introduction

This study was prompted by a young man with multiple sclerosis (MS) who
used marihuana as a remedy for his various motor, micturition and sexual
handicaps. After smoking a marihuana cigarette on the ward, he clinically
improved. He agreed to the beneficial effects of marihuana being
investigated by means of quantitative clinical and electrophysiological
assessment.

Case Report

This male patient, born in 1955, had had MS since 1983. At the time of our
experiments he was bound to a wheelchair because of severe limb and gait
ataxia and spastic tetraparesis. After micturition, his residual urine
volume was 100-150 ml. He complained of impotence, with erections lasting
less than 5 min and lacking ejaculation. He tried a marihuana cigarette in
about 1984 and noted an instantaneous improvement of his motor and sexual
functions lasting for several days. Since then, he regularly took some
marihuana biscuits each week, which enabled him to climb stairs, to walk on
even ground, and to have erections for more than 30 min. allowing him a
quite satisfactory sexual life.

Methods

>From 12 October 1985 the patient abstained from all drugs, including
marihuana. He was hospitalized between 17 October and 25 October. On 22
October, one "experimental" marihuana cigarette was allowed, and various
electrophysiological experiments were performed as described below.

Clinical rating was performed daily by the same neurologist and on 22
October before and after the "experimental" cigarette. Rating comprised
motor functions relevant to the electrophysiological tests described below
(see Fig. 1).

The flexor reflex was elicited by a painful electrical shock to the
foot sole and recorded from the quadriceps (Q), posterior biceps (PB),
gastrocnemius (G) and tibialis anterior (TA) muscles. The EMG was
full-wave rectified, and eight consecutive reflexes were summated. Five
control series of eight consecutive reflexes were run at intervals of about
5 min. The patient was then asked to take one whiff of his "experimental"
cigarette, and further series of reflexes were run in the manner described
above (for details see [12]).

Finger movements were recorded in a standardized pointing task
performed before and after both the "experimental" cigarette and the flexor
reflex experiment. Basically, the recording device consisted of a
three-coil-transmitter system generating non-homogeneous magnetic fields,
and a miniaturized receiver coil attached to the finger tip. When the
finger moved through the magnetic fields a signal was induced in the
receiver coil, allowing the computation of the two-dimensional movement
trajectory (for details see [15]). Ten trials were performed before and
after marihuana smoking, each consisting of a pointing movement of the
right index finger over a 10-cm distance. The forearm rested on a stable
support, but the finger and hand could not reach the target.

Results

Clinical rating showed a moderate deterioration of motor functions between
17 October and 22 October (Fig. 1) On 22 October, before the
"experimental" cigarette, he was incapable of walking a few steps even with
support: his muscle force in the legs did not exceed MRC grade 3. Muscle
tone ranged between slightly and moderately increased, and the leg deep
tendon reflexes were exaggerated or clonic with sustained ankle and knee
clonus. The receptive field of the Babinski sign covered the whole foot
and the shin. Ataxia in the arms was severe and could not be tested in the
legs because of distinct hip flexor paresis.

About 145 min after the marihuana cigarette, muscle force was
somewhat increased in the knee extensors and ankle flexors (but not in the
hip flexors), and muscle tone was reduced. The leg deep tendon reflexes
showed normalization, too, corresponding to a clear shortening of the
periods of clonus. The receptive field of the Babinski sign was confined
to the lateral foot sole margin. Ataxia in finger-nose testing was
moderate. After the flexor reflex experiment, the patient was able to walk
a few metres between the couch and his wheelchair with support. Some of
these improvements lasted beyond 23 October and even 24 October (Fig 1).

The flexor reflex showed the desynchronized and prolonged reflex
pattern typical of spastic paresis (Fig. 2a: cf [13]). As soon as 2 min
after the whiff of the marihuana cigarette, a clear attenuation of the
reflex activity was noted. Attenuation was about equal in all four muscles
(20%-30% of the last three control recordings) and progressed until 17 min
after the whiff. A second whiff (18 min after the first one) did not
induce further reflex attenuation. Single sweep recordings showed that the
reflex attenuation after marihuana was not due to enhanced habituation;:
after marihuana even the first of the eight consecutive reflex responses
was attenuated.

Electromagnetic recording of action tremor revealed a coarse 3 Hz
hand and finger tremor with an amplitude between 1 and 3 cm, persisting
throughout nearly the whole movement. Hours after the "experimental"
cigarette, action tremor was almost completely abolished, although the
movements were made at about the same speed (Fig. 2b).

Discussion

Our findings clearly show that there are indeed motor actions of marihuana
which were (a) reproducible in a laboratory situation most exhaustive to
the patient. (b) quantitatively assessable by means of electrophysiological
testing, and (c) in line with the results of clinical rating. Our findings
further correspond with earlier anecdotal clinical reports [4, 6, 11, 14].
Little is known about the neurophysiological background of the
antispastic and antiataxic actions of marihuana seen in our patient.
However, some findings in experimental animals seem relevant to our
observations. Cannabinoids in higher dosages attenuate the monosynaptic
reflex [1,2,17,18] principally corresponding to the attenuation of both
deep tendon reflexes and clonus in our patient (Fig. 1). Polysynaptic
reflexes were also attenuated after tetrahydrocannabinol derivatives in
experimental animals [1, 7, 20], fitting in well with the narrowing of the
receptive field of the Babinski sign (Fig. 1) and with the results of our
flexor reflex experiment. As cannabinoids have analgesic properties
[16,20], attenuation of the pathological flexor reflex in the present case
could represent analgesic rather than antispastic effects of the drug.
However, analgesic effects are also attributed to several antispastic drugs
[10,21] and, on the other hand, classical analgesics such as opioids may
improve spastic symptoms [19]. One might, therefore, indeed wonder whether
both the antispastic and analgesic actions of such drugs are in fact at
least to a substantial degree based on common neuronal mechanisms such as
an increase of presynaptic inhibition or a decrease of postsynaptic
excitation of multireceptive interneurones at various levels of the
neuraxis. Whatever the mechanism, the antispastic actions of marihuana in
both clinical rating and electrophysiological testing are similar to those
seen in spastic patients after either 0.3 mg tizanidine [13], 150 mcg
clonidine, or 10 mg diazepam (unpublished observations). The important
difference is that marihuana apparently also has antiataxic actions (Fig.
2b: see also [4] not ascribed to any antispastic drug.

The biochemical basis of the motor effects of marihuana is obscure.
Available data, although somewhat controversial, suggest that cannabinoids
release brain serotonin from its storage sites and block its re-uptake [8],
inhibit the synthesis of prostaglandins within the CNS [9] and-- in large
doses -- elevate brain acetylcholine and reduce its utilization [5]. The
relationship of these neurotransmitters to spasticity and ataxia is
unknown: none of the well-established antispastic drugs is thought to
interfere with them; they are only scarcely, if at all, found within the
cerebellum [3].

Acknowledgement. We thank our patient for his kind cooperation throughout
this study.

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Received November 30, 1987/ Received in revised form October 6, 1988/
Accepted November 6, 1988

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