Denis Petro, M.D., is a practicing neurologist and clinical drug researcher in Arlington, Virginia.

 

Background

 

A seizure is a transient disturbance of cerebral function due to excessive neuronal production of an excitatory neurotransmitter. The term epilepsy is used to refer to a condition characterized by recurrent seizures. In the United States the more than 1 million patients who suffer from seizures without obvious intercurrent causative illness represent a continuing challenge to the physician. While medical management of epilepsy has improved over the years, at least 20 percent of patients remain under unsatisfactory control.

 

Our understanding of the etiology of seizure disorders has advanced significantly over the past hundred years beginning with the work of Hughlings Jackson in the nineteenth century. Seizures can be due to many factors including congenital abnormalities and perinatal injuries, metabolic disorders, trauma, tumors, vascular diseases, degenerative disorders or infection. Regarding patients with seizures that have no specific cause, the term idiopathic epilepsy is used.

 

While seizures can be described in different ways, the International League Against Epilepsy has classified seizures based on clinical and electroencephalographic features. The classification begins by dividing seizures into those that are generalized without focal features and those that are partial by beginning in one hemisphere. Generalized seizures include tonic-clonic (grand mal) seizures, absence (petit mal), and myoclonic attacks. Partial seizures include simple partial seizures manifested in focal motor or somatosensory symptoms. Complex partial seizures may begin as simple partial seizures but include cognitive, affective, and psychomotor symptoms and involve impaired consciousness.

 

While the manifestations of seizures can vary, the fundamental cause of seizures is thought to involve abnormalities of cerebral neurotransmitters. Excessive excitatory neurotransmission or impaired neuronal inhibition can be implicated in causing seizure disorders. The goal of therapy is to decrease excitation or to prevent the spread of the localized abnormality. Significant advances in the treatment of seizure disorders have been made in the past 50 years. The choice of anticonvulsant drug is based on the classification of the seizure type and the clinical experience with individual drugs. The most commonly used anticonvulsants are phenytoin, carbamazepine, phenobarbital, and valproic acid. The patient is usually treated with one of these drugs, and the dosage is increased slowly until seizures are controlled or side effects limit further increases. Plasma drug levels are monitored to check patient compliance and to assure that blood concentrations of the drug are within the generally accepted therapeutic range. In uncomplicated cases, control of seizures can be achieved with a single drug. In uncontrolled cases, a second drug can be added to reduce the severity and frequency of seizures. Unfortunately, many patients cannot tolerate multiple drugs without serious side effects.

 

An estimated 20 percent to 30 percent of patients with seizures do not achieve acceptable seizure control with conventional medical management. An option to consider in some patients with a focal seizure disorder is surgical excision of the excitatory lesion. Major neurologic centers have reported promising results with this technique, which includes careful EEG mapping to localize the lesion. At one center (Montreal), one-third of the patients became free of seizures, and another third noted a marked reduction in seizures after surgery. Several new anticonvulsants (gabapentin and felbamate) will become available in the near future pending final regulatory action, and these new drugs offer new hope to those patients whose seizures are not adequately managed with conventional treatment.

 

Marijuana in Seizure Disorders

 

Marijuana has been used as an anticonvulsant since ancient times in the Middle and Far East. In the nineteenth century cannabis extracts were widely used in India to treat seizures of varying causes. In modern times a few reports with mixed results have been published. Since marijuana contains many individual cannabinoids with differing psychoactive potentials, a clear picture of the role of marijuana in the treatment of epilepsy does not yet exist. Several case histories have been published that either suggest marijuana as a potential beneficial drug in epilepsy or implicate marijuana as a risk factor that increases seizures. In the mid-1970s a survey of illegal drug use at an outpatient epilepsy clinic was reported. Of the patients under 30 years of age 29 percent reported using marijuana. When asked what effect marijuana had on their symptoms, most reported no effect. One patient reported a decrease in seizures while using marijuana, and one patient reported that marijuana "caused" his seizures.

 

While little else has been published concerning the effect of marijuana on clinical seizures, studies of individual cannabinoids have been reported for delta-9-THC and cannabidiol (CBD). Seizures have been reported in patients after they used THC to control nausea in cancer chemotherapy. Since THC is psychoactive in many animal studies and is associated with other adverse effects, THC can be eliminated from consideration as a potential candidate for the treatment of epilepsy. In animal seizure models CBD has been shown to have anticonvulsant properties with potential in grand mal, cortical focal, and complex partial seizures. In a clinical study of patients with secondary generalized epilepsy with temporal focus, CBD was administered for up to four and a half months in eight patients (Cunha et al. 1980). Four of the eight subjects were considered to be improved, three were partially improved, and one did not improve while receiving CBD. No serious side effects were reported.

 

In summary, a review of the literature documents some reports of the effects of marijuana in seizure disorders. The data concerning marijuana is mixed with both positive and negative reports. The scientific evidence in support of CBD is stronger based on both preclinical and clinical studies (Carlini and Cunha 1981; Consroe et al. 1981; Consroe et al. 1975; Cunha et al. 1980; Karler and Turkanis 1981).

 

Clinical Experience

 

Over the past decade, individuals with seizure disorders who claimed to have benefited from marijuana have been contacted either to assist them in FDA regulatory filings or in association with legal proceedings after arrest. So far, 11 cases have been reviewed via personal telephone communication, medical record review and discussion with attending physicians. While no serious medical conclusions can be drawn, several observations are of interest. All cases are males ranging in age from 19 to 43 years. In cases in which a diagnostic classification is available, five of seven were reported to have complex partial seizures with secondary generalization. While conventional anticonvulsants were used in all cases, drug levels were not available in most cases. In cases associated with litigation, the question of compliance with the attending physician's clinical recommendations has been a recurrent difficulty. Since the medical literature is somewhat ambiguous concerning marijuana and epilepsy, a convincing argument in support of individuals who make a therapeutic claim in this area is weakened. In addition, with the anticipated arrival of new anticonvulsants, which have their advocates, support for the use of marijuana in epilepsy is undermined. However, even with this background, in selected cases of complex partial seizures the evidence for a therapeutic benefit of marijuana is enticing and should not be disregarded. With the possibility for a change in governmental policy concerning the therapeutic use of marijuana, one should not be discouraged in pursuit of improved control of seizure disorders by this medication.

 

References

 

Carlini, E.A. and J.M. Cunha. 1981. Hypnotic and anti-epileptic effects of cannabidiol. Journal of Clinical Pharmacology 21 Supplement (8 and 9): 417S-421S.

Consroe, P., A. Martin, and V. Singh. 1981. Antiepileptic potential of cannabidiol analogs. Journal of Clinical Pharmacology 21 Supplement (8 and 9): 428S-436S.

Consroe, P., and S. Snider. 1986. Therapeutic potential of cannabinoids in neurological disorders. In Cannabinoids as Therapeutic Agents, ed. R. Mechoulam, 22-49. Boca Raton, FL: CRC Press.

Consroe, P.F., G.C. Wood, and H. Buchsbaum. 1975. Anticonvulsant nature of marihuana smoking. Journal of the American Medical Association 234 (3): 306-307.

Cunha, J.M., E.A. Carlini, A.E. Pereira, O.L. Ramos, C. Pimentel, R. Gagliardi, W.L. Sanvito, N. Lander, and R. Mechoulam. 1980. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21: 175-185.

Feeney, D. 1976. Marihuana use among epileptics. Journal of the American Medical Association 235: 1105.

Karler, R., and S.A. Turkanis. 1981. The cannabinoids as potential antiepileptics. Journal of Clinical Pharmacology 21 Supplement (8 and 9): 437S-448S.

Savaki, H.E., J.M. Cunha, E.A. Carlini, and T.A. Kephalas. 1976. Pharmacological activity of 3 fractions obtained by smoking cannabis through a water pipe. Bulletin on Narcotics 28 (2): 49-56.