Jacob Bell
New Member
J. C. Brust, S. K. Ng, A. W. Hauser, and M. Susser
Department of Neurology, Harlem Hospital Center, New York, NY.
INTRODUCTION
Marijuana is the most widely used illicit drug in the United States (1).
Animal and human studies of its effects on seizures have been conflicting
(2, 3). To determine if marijuana is a risk factor for new onset seizures,
we conducted a case control study at Harlem Hospital Center in New
York City.
METHODS
Cases consisted of 308 patients over 15 years of age admitted with new
onset seizures between December 1981 and February 1984. Childhood
febrile seizures were not counted as previous seizures, and we included
as new onset seizures those occurring within the previous 12 months but
never evaluated medically. Seizures were classified as generalized (n =
193), partial (n = 89), or unclassified (n = 26) and by antecedents as
either provoked (n = 81) or unprovoked (n = 227). Provoked seizures
were those associated with acute metabolic derangements, stroke within
7 days of seizure onset, CNS infection, brain tumor, intravenous administration
of epileptogenic drugs within an hour of the seizure, severe head
trauma within 7 days of seizure onset, and body temperature exceeding
40.5 C (Table 1).
Controls were 294 patients admitted for the first time with an acute
surgical condition (Table 2). Patients and controls were interviewed
using a questionnaire that covered medical and medication history as
well as use of alcohol, tobacco, and illicit drugs. Missing data for any
variable occurred in less than 4 percent of subjects. For categorical
exposure variables a missing entry was classified as unexposed. Statistical
analysis included multiple logistic regression to adjust for potential
confounders such as age, sex, head trauma, stroke, alcohol, and polydrug
abuse.
* From the Department of Neurology, Harlem Hospital Center, and the GH Sergievsky
Center, Columbia University College of Physicians & Surgeons, New York, NY 10037.
RESULTS
Marijuana was the illicit drug most often reported by cases and
controls, and among men its use was significantly less for cases than
controls (28.9 percent vs. 40.6 percent, p < 0.05) (Table 3). Among
women a smaller nonsignificant difference existed in the same direction
(11.7 percent vs 15.2 percent). Use of other illicit drugs and alcohol was
frequent among marijuana users. Frequency and duration of marijuana
use was similar among cases and controls: about a third were daily users
and two thirds were weekly users; 70 percent had used marijuana for at
least 2 years and 50 percent for at least 5 years.
Reported use of marijuana at any time was less among all seizure
patients than controls, but the adjusted odds ratio (OR) of 0.66 (95
percent confidence interval (CI) 0.39-1.12) was not statistically significant.
Among men with unprovoked seizures, however, marijuana use was
significantly less frequent (adjusted OR = 0.42, 95 percent CI 0.22-
0.82)-ie marijuana use was protective. This effect was limited to those
who had never used heroin. Marijuana use within 90 days of hospitali-
zation carried an even lower odds ratio and in non-heroin-using men was
protective for both unprovoked and provoked seizures. Among women
marijuana use was much less prevalent than among men, and although
use was greater among controls than cases, there was no statistically
significant protective effect for either use at any time or use within 30
days.
DISCUSSION
The protective effect of marijuana against new onset seizures is particularly
striking in that marijuana use was positively correlated with other
risk factors such as alcohol and heroin, which would tend to bias toward
finding marijuana use a risk factor. Use within 30 days was protective in
men for both unprovoked and provoked seizures. The lack of demonstrable
protection in women might be attributable to the smaller number of
users.
Marijuana contains numerous cannabinoid compounds, and animal
studies have demonstrated their different pro- and anticonvulsant properties.
In animal studies delta-9-tetrahydrocannabinol (THC), the major
psychoactive compound in marijuana, has been either epileptogenic (4-
8) or anticonvulsant (9-16) or had no effect on seizures, (13, 14, 17)
depending on the species and experimental design. A strain of New
Zealand rabbits is uniquely susceptible to seizures induced by THC and
other similarly psychoactive cannabinoids (4, 8, 18, 19). THC protected
chickens from photic-induced but not pentylenetetrazol (PTZ)-induced
seizures (13). In mice THC was anticonvulsant for maximal electroshock
seizures but proconvulsant for PTZ- and strychnine-induced seizures
(20). In cats THC prevented kindled amygdaloid seizures if given early
but not if given after seizures were partially or fully developed (15). In
baboons THC blocked established kindled amygdaloid seizures but not
photic-induced seizures (15). In genetically seizure-prone gerbils THC
was anticonvulsant, but tolerance developed to this effect (16).
Cannabidiol (CBD), a non-psychoactive cannabinoid, has been more
consistently anticonvulsant in a variety of experimental settings, (6-9,
21-23) as have some other non-psychoactive cannabinoids (3, 22, 24-26).
In studies of transcallosal cortical evoked response in rats and spinal
monosynaptic reflexes in cats, low doses of THC enhanced synaptic
transmission, whereas higher doses of THC and all doses of CBD caused
only depression (7). In rats CBD was anticonvulsant for both maximal
electroshock and audiogenic seizures and enhanced the anticonvulsant
potency of phenytoin while antagonizing that of ethosuximide, clonazepam,
and trimethadione (27). Although CBD and phenytoin are effective
against similar types of seizures, electrophysiologic studies suggest they
have different mechanisms of action (3). The anticonvulsant effectiveness
of Cannabis indica resin against maximal electroshock seizures in
rats was inhibited by reserpine, and this inhibition was reversed by the
serotonin precursor 5-hydroxytryptophan (28).
Marijuana's anticonvulsant properties were noted in the fifteenth
century (29), yet few studies have been conducted in humans (2, 30-37).
In a single case report marijuana smoking was reported to be necessary
for seizure control (2). A New Mexico survey of 42 epileptics under age
30 found that 29% used marijuana; one subject reported that marijuana
decreased seizures and another that it "caused" them (35). In another
case report intravenous CBD did not alter (and maybe even increased)
the electroencephalographic spike and wave abnormalities of a young
man with well-controlled "tonic clonic seizures" (36). There has been
only one prospectively designed treatment study, a double-blind placebocontrolled
trial of patients refractory to other drugs. CBD, given to 8 of
the 16 patients, acutely exacerbated electroencephalographic but not
behavioral seizures. After 4 to 5 months, however, 7 of 8 patients receiving
CBD were electroencephalographically and behaviorally seizure-free
compared to 1 of 8 controls. The only sign of toxicity was somnolence
(37).
In conclusion, marijuana is protective against new onset seizures, and
this effect is consistent with previous studies in animals and humans.
Whatever the mechanisms, these findings imply that among marijuana's
cannabinoid compounds are potentially useful anticonvulsant drugs.
REFERENCES
1. Brust JCM: Drug dependence. In: Baker AB, Joynt RJ (Eds): Clinical Neurology,
Volume 2, Harper & Row, Philadelphia, 1986, Chapter 21, pp 1-92.
2. Consroe PF, Wood GC, Buchsbaum H: Anticonvulsant nature of marijuana smoking.
JAMA 1975; 234: 306.
3. Karler R, Turkanis SA: The cannabinoids as potential antiepileptics. J Clin Phamacol
1981; 21: 437S.
4. Fish BS, Consroe P, Fox RR: Inheritance of delta-9-tetrahydrocannabinol seizure
susceptibility in rabbits. J Hered 1981; 72: 215.
5. Turkanis SA, Karler R: Central excitatory properties of delta-9-tetrahydrocannabinol
and its metabolites in iron-induced epileptic rats. Neuropharmacology 1982; 21: 7.
6. Chiu P, Olsen DM, Borys HK, Karler R, Turkanis SA: The influence of cannabidiol
and delta-9-tetrahydrocannabinol on cobalt epilepsy in rats. Epilepsia 1979; 20: 365.
7. Turkanis SA, Karler R: Electrophysiologic properties of the cannabinoids. J Clin
Pharmacol 1981; 21 (Suppl.): 449S.
8. Consroe P, Martin P, Eisenstein D: Anticonvulsant drug antagonism of delta-9-
tetrahydrocannabinol-induced seizures in rabbits. Res Commun Chem Pathol Pharmacol
1977; 16: 1.
9. Turkanis SA, Smiley KA, Borys HK, Olsen DM, Karler R: An electrophysiological
analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious
rats. Epilepsia 1979; 20: 351.
10. Colasanti BK, Lindamood C, Craig CR: Effects of marijuana cannabinoids of seizure
activity in cobalt-epileptic rats. Pharmacol Biochem Behav 1982; 16: 573.
11. Corcoran ME, McCaughran JA, Wada JA: Antiepileptic and prophylactic effects of
tetrahydrocannabinols in amygdaloid kindled rats. Epilepsia 1978; 19: 46.
12. Karler R, Turkanis SA: Subcute cannabinoid treatment: anticonvulsant activity and
withdrawal excitability in mice. Br J Pharmacol 1980; 68: 479.
13. Johnson DD, McNeill JR, Crawford RD, Wilcox WC: Epileptiform seizures in domestic
fowl. V. The anticonvulsant activity of delta-9-tetrahydrocannabinol. Can J Physiol
Pharmacol 1975; 53: 1007.
14. Wada JA, Osawa T, Corcoran ME: Effects of tetrahydrocannabinols on kindled
amygdaloid seizures in Senegalese baboons, Papio papio. Epilepsia 1975; 16: 439.
15. Wada JA, Wake A, Dato M, Corcoran ME: Antiepileptic and prophylactic effects of
tetrahydrocannabinols in amygdaloid kindled rats. Epilepsia 1975; 16: 503.
16. Ten-Harn M, Laskota WJ, Lomak P: Acute and chronic effects of beta-9-tetrahydrocannabinol
on seizures in the gerbil. Eur J Pharmacol 1975; 31: 148.
17. Meldrum BS, Fariello RG, Puil EA, Derovaus M, Naquet R: Delta-9-tetrahydrocannabinol
and epilepsy in the photosensitive baboon, Papio papio. Epilepsia 1974; 15:
255.
18. Fish BS, Consroe P: The ontogeny of delta-tetrahydrocannabinol responsiveness in the
rabbit. Dev Psychobiol 1983; 16: 147.
19. Consroe P, Martin AR, Fish BS: Use of a potential rabbit model for structure-behavioral
activity studies of cannabinoids. J Med Chem 1982; 25: 596.
20. Sofia RD, Solomon TA, Barry H: Anticonvulsant activity of delta-9-tetrahydrocannabinol
compared with three other drugs. Eur J Pharmacol 1976; 35: 7.
21. Consroe P, Benedito MA, Leite JR, Carlini EA, Mechoulam R: Effects of cannabidiol
on behavioral seizures caused by convulsant drugs or current in mice. Eur J Pharmacol
1982; 83: 293.
22. Consroe P, Martin A, Singh V: Antiepileptic potential of cannabidiol. J Clin Pharmacol
1981; 21 (Suppl): 428S.
23. Izquierdo I, Tannhauser M: The effect of cannabidiol on maximal electroschok seizures
in rats. J Pharm Pharmacol 1973; 25: 916.
24. Ehlers CL, Henrikson SJ, Bloom FR: Levonantradol potentates the anticonvulsant
effects of diazepam and valproic acid in the kindling model of epilepsy. J Clin Pharmacol
1981; 21 (Suppl): 406S.
25. Razdan RK, Terris BZ, Pars HG, et al: Drugs derived from cannabinoids. 2. Basic
esters of nitrogen and carbocyclic analogs. J Med Chem 1976; 19: 454.
26. Karler R, Cely W, Turkanis SA: The anticonvulsant activity of cannabidiol and
cannabinol. Life Sci 1974; 15: 931.
27. Consroe P, Wolkin A: Cannabidiol-antiepileptic drug comparisons and interactions
in experimentally induced seizures in rats. J Pharmacol Exp Ther 1977; 20: 26.
28. Ghosh P, Bhattacharya SK: Anticonvulsant action of cannabis in the rat: role of brain
monoamines. Psychopharmacology 1978; 59: 293.
29. Mechoulam R, Carlini EA: Toward drugs derived from cannabis. Naturwissenschaften
1978; 65: 174.
30. O'Shausghnessy WB: On the preparation of Indian hemp or gunjah. Trans Med Phys
Soc Bombay 1842; 8: 421.
31. Reynolds JR: Therapeutic uses and toxic effects of Cannabis indica. Lancet 1980; 1:
637.
32. Davis JP, Ramsey HH: Antiepileptic actions of marijuana-active substances. Fed Proc
1949; 8: 284.
33. Karler R, Turkanis SA: Cannabis and epilepsy. Adv Biosci 1978; 22-23: 619.
34. Feeney DM. Marijuana and epilepsy: paradoxical anticonvulsant and convulsant effects.
Adv Biosci 1978; 22-23: 643.
35. Feeney DM: Marijuana use among epileptics. JAMA 1976; 235: 1105.
36. Perez-Reyes M, Wingfield M: Cannabidiol and electroencephalographic epileptic activity.
JAMA 1974; 230: 1635.
37. Cunha JM, Carlini EA, Pereira AE, et al: Chronic administration of cannabidiol to
healthy volunteers and epileptic patients. Pharmacology 1980; 21: 175
Source: Marijuana Use And The Risk Of New Onset Seizures
Department of Neurology, Harlem Hospital Center, New York, NY.
INTRODUCTION
Marijuana is the most widely used illicit drug in the United States (1).
Animal and human studies of its effects on seizures have been conflicting
(2, 3). To determine if marijuana is a risk factor for new onset seizures,
we conducted a case control study at Harlem Hospital Center in New
York City.
METHODS
Cases consisted of 308 patients over 15 years of age admitted with new
onset seizures between December 1981 and February 1984. Childhood
febrile seizures were not counted as previous seizures, and we included
as new onset seizures those occurring within the previous 12 months but
never evaluated medically. Seizures were classified as generalized (n =
193), partial (n = 89), or unclassified (n = 26) and by antecedents as
either provoked (n = 81) or unprovoked (n = 227). Provoked seizures
were those associated with acute metabolic derangements, stroke within
7 days of seizure onset, CNS infection, brain tumor, intravenous administration
of epileptogenic drugs within an hour of the seizure, severe head
trauma within 7 days of seizure onset, and body temperature exceeding
40.5 C (Table 1).
Controls were 294 patients admitted for the first time with an acute
surgical condition (Table 2). Patients and controls were interviewed
using a questionnaire that covered medical and medication history as
well as use of alcohol, tobacco, and illicit drugs. Missing data for any
variable occurred in less than 4 percent of subjects. For categorical
exposure variables a missing entry was classified as unexposed. Statistical
analysis included multiple logistic regression to adjust for potential
confounders such as age, sex, head trauma, stroke, alcohol, and polydrug
abuse.
* From the Department of Neurology, Harlem Hospital Center, and the GH Sergievsky
Center, Columbia University College of Physicians & Surgeons, New York, NY 10037.
RESULTS
Marijuana was the illicit drug most often reported by cases and
controls, and among men its use was significantly less for cases than
controls (28.9 percent vs. 40.6 percent, p < 0.05) (Table 3). Among
women a smaller nonsignificant difference existed in the same direction
(11.7 percent vs 15.2 percent). Use of other illicit drugs and alcohol was
frequent among marijuana users. Frequency and duration of marijuana
use was similar among cases and controls: about a third were daily users
and two thirds were weekly users; 70 percent had used marijuana for at
least 2 years and 50 percent for at least 5 years.
Reported use of marijuana at any time was less among all seizure
patients than controls, but the adjusted odds ratio (OR) of 0.66 (95
percent confidence interval (CI) 0.39-1.12) was not statistically significant.
Among men with unprovoked seizures, however, marijuana use was
significantly less frequent (adjusted OR = 0.42, 95 percent CI 0.22-
0.82)-ie marijuana use was protective. This effect was limited to those
who had never used heroin. Marijuana use within 90 days of hospitali-
zation carried an even lower odds ratio and in non-heroin-using men was
protective for both unprovoked and provoked seizures. Among women
marijuana use was much less prevalent than among men, and although
use was greater among controls than cases, there was no statistically
significant protective effect for either use at any time or use within 30
days.
DISCUSSION
The protective effect of marijuana against new onset seizures is particularly
striking in that marijuana use was positively correlated with other
risk factors such as alcohol and heroin, which would tend to bias toward
finding marijuana use a risk factor. Use within 30 days was protective in
men for both unprovoked and provoked seizures. The lack of demonstrable
protection in women might be attributable to the smaller number of
users.
Marijuana contains numerous cannabinoid compounds, and animal
studies have demonstrated their different pro- and anticonvulsant properties.
In animal studies delta-9-tetrahydrocannabinol (THC), the major
psychoactive compound in marijuana, has been either epileptogenic (4-
8) or anticonvulsant (9-16) or had no effect on seizures, (13, 14, 17)
depending on the species and experimental design. A strain of New
Zealand rabbits is uniquely susceptible to seizures induced by THC and
other similarly psychoactive cannabinoids (4, 8, 18, 19). THC protected
chickens from photic-induced but not pentylenetetrazol (PTZ)-induced
seizures (13). In mice THC was anticonvulsant for maximal electroshock
seizures but proconvulsant for PTZ- and strychnine-induced seizures
(20). In cats THC prevented kindled amygdaloid seizures if given early
but not if given after seizures were partially or fully developed (15). In
baboons THC blocked established kindled amygdaloid seizures but not
photic-induced seizures (15). In genetically seizure-prone gerbils THC
was anticonvulsant, but tolerance developed to this effect (16).
Cannabidiol (CBD), a non-psychoactive cannabinoid, has been more
consistently anticonvulsant in a variety of experimental settings, (6-9,
21-23) as have some other non-psychoactive cannabinoids (3, 22, 24-26).
In studies of transcallosal cortical evoked response in rats and spinal
monosynaptic reflexes in cats, low doses of THC enhanced synaptic
transmission, whereas higher doses of THC and all doses of CBD caused
only depression (7). In rats CBD was anticonvulsant for both maximal
electroshock and audiogenic seizures and enhanced the anticonvulsant
potency of phenytoin while antagonizing that of ethosuximide, clonazepam,
and trimethadione (27). Although CBD and phenytoin are effective
against similar types of seizures, electrophysiologic studies suggest they
have different mechanisms of action (3). The anticonvulsant effectiveness
of Cannabis indica resin against maximal electroshock seizures in
rats was inhibited by reserpine, and this inhibition was reversed by the
serotonin precursor 5-hydroxytryptophan (28).
Marijuana's anticonvulsant properties were noted in the fifteenth
century (29), yet few studies have been conducted in humans (2, 30-37).
In a single case report marijuana smoking was reported to be necessary
for seizure control (2). A New Mexico survey of 42 epileptics under age
30 found that 29% used marijuana; one subject reported that marijuana
decreased seizures and another that it "caused" them (35). In another
case report intravenous CBD did not alter (and maybe even increased)
the electroencephalographic spike and wave abnormalities of a young
man with well-controlled "tonic clonic seizures" (36). There has been
only one prospectively designed treatment study, a double-blind placebocontrolled
trial of patients refractory to other drugs. CBD, given to 8 of
the 16 patients, acutely exacerbated electroencephalographic but not
behavioral seizures. After 4 to 5 months, however, 7 of 8 patients receiving
CBD were electroencephalographically and behaviorally seizure-free
compared to 1 of 8 controls. The only sign of toxicity was somnolence
(37).
In conclusion, marijuana is protective against new onset seizures, and
this effect is consistent with previous studies in animals and humans.
Whatever the mechanisms, these findings imply that among marijuana's
cannabinoid compounds are potentially useful anticonvulsant drugs.
REFERENCES
1. Brust JCM: Drug dependence. In: Baker AB, Joynt RJ (Eds): Clinical Neurology,
Volume 2, Harper & Row, Philadelphia, 1986, Chapter 21, pp 1-92.
2. Consroe PF, Wood GC, Buchsbaum H: Anticonvulsant nature of marijuana smoking.
JAMA 1975; 234: 306.
3. Karler R, Turkanis SA: The cannabinoids as potential antiepileptics. J Clin Phamacol
1981; 21: 437S.
4. Fish BS, Consroe P, Fox RR: Inheritance of delta-9-tetrahydrocannabinol seizure
susceptibility in rabbits. J Hered 1981; 72: 215.
5. Turkanis SA, Karler R: Central excitatory properties of delta-9-tetrahydrocannabinol
and its metabolites in iron-induced epileptic rats. Neuropharmacology 1982; 21: 7.
6. Chiu P, Olsen DM, Borys HK, Karler R, Turkanis SA: The influence of cannabidiol
and delta-9-tetrahydrocannabinol on cobalt epilepsy in rats. Epilepsia 1979; 20: 365.
7. Turkanis SA, Karler R: Electrophysiologic properties of the cannabinoids. J Clin
Pharmacol 1981; 21 (Suppl.): 449S.
8. Consroe P, Martin P, Eisenstein D: Anticonvulsant drug antagonism of delta-9-
tetrahydrocannabinol-induced seizures in rabbits. Res Commun Chem Pathol Pharmacol
1977; 16: 1.
9. Turkanis SA, Smiley KA, Borys HK, Olsen DM, Karler R: An electrophysiological
analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious
rats. Epilepsia 1979; 20: 351.
10. Colasanti BK, Lindamood C, Craig CR: Effects of marijuana cannabinoids of seizure
activity in cobalt-epileptic rats. Pharmacol Biochem Behav 1982; 16: 573.
11. Corcoran ME, McCaughran JA, Wada JA: Antiepileptic and prophylactic effects of
tetrahydrocannabinols in amygdaloid kindled rats. Epilepsia 1978; 19: 46.
12. Karler R, Turkanis SA: Subcute cannabinoid treatment: anticonvulsant activity and
withdrawal excitability in mice. Br J Pharmacol 1980; 68: 479.
13. Johnson DD, McNeill JR, Crawford RD, Wilcox WC: Epileptiform seizures in domestic
fowl. V. The anticonvulsant activity of delta-9-tetrahydrocannabinol. Can J Physiol
Pharmacol 1975; 53: 1007.
14. Wada JA, Osawa T, Corcoran ME: Effects of tetrahydrocannabinols on kindled
amygdaloid seizures in Senegalese baboons, Papio papio. Epilepsia 1975; 16: 439.
15. Wada JA, Wake A, Dato M, Corcoran ME: Antiepileptic and prophylactic effects of
tetrahydrocannabinols in amygdaloid kindled rats. Epilepsia 1975; 16: 503.
16. Ten-Harn M, Laskota WJ, Lomak P: Acute and chronic effects of beta-9-tetrahydrocannabinol
on seizures in the gerbil. Eur J Pharmacol 1975; 31: 148.
17. Meldrum BS, Fariello RG, Puil EA, Derovaus M, Naquet R: Delta-9-tetrahydrocannabinol
and epilepsy in the photosensitive baboon, Papio papio. Epilepsia 1974; 15:
255.
18. Fish BS, Consroe P: The ontogeny of delta-tetrahydrocannabinol responsiveness in the
rabbit. Dev Psychobiol 1983; 16: 147.
19. Consroe P, Martin AR, Fish BS: Use of a potential rabbit model for structure-behavioral
activity studies of cannabinoids. J Med Chem 1982; 25: 596.
20. Sofia RD, Solomon TA, Barry H: Anticonvulsant activity of delta-9-tetrahydrocannabinol
compared with three other drugs. Eur J Pharmacol 1976; 35: 7.
21. Consroe P, Benedito MA, Leite JR, Carlini EA, Mechoulam R: Effects of cannabidiol
on behavioral seizures caused by convulsant drugs or current in mice. Eur J Pharmacol
1982; 83: 293.
22. Consroe P, Martin A, Singh V: Antiepileptic potential of cannabidiol. J Clin Pharmacol
1981; 21 (Suppl): 428S.
23. Izquierdo I, Tannhauser M: The effect of cannabidiol on maximal electroschok seizures
in rats. J Pharm Pharmacol 1973; 25: 916.
24. Ehlers CL, Henrikson SJ, Bloom FR: Levonantradol potentates the anticonvulsant
effects of diazepam and valproic acid in the kindling model of epilepsy. J Clin Pharmacol
1981; 21 (Suppl): 406S.
25. Razdan RK, Terris BZ, Pars HG, et al: Drugs derived from cannabinoids. 2. Basic
esters of nitrogen and carbocyclic analogs. J Med Chem 1976; 19: 454.
26. Karler R, Cely W, Turkanis SA: The anticonvulsant activity of cannabidiol and
cannabinol. Life Sci 1974; 15: 931.
27. Consroe P, Wolkin A: Cannabidiol-antiepileptic drug comparisons and interactions
in experimentally induced seizures in rats. J Pharmacol Exp Ther 1977; 20: 26.
28. Ghosh P, Bhattacharya SK: Anticonvulsant action of cannabis in the rat: role of brain
monoamines. Psychopharmacology 1978; 59: 293.
29. Mechoulam R, Carlini EA: Toward drugs derived from cannabis. Naturwissenschaften
1978; 65: 174.
30. O'Shausghnessy WB: On the preparation of Indian hemp or gunjah. Trans Med Phys
Soc Bombay 1842; 8: 421.
31. Reynolds JR: Therapeutic uses and toxic effects of Cannabis indica. Lancet 1980; 1:
637.
32. Davis JP, Ramsey HH: Antiepileptic actions of marijuana-active substances. Fed Proc
1949; 8: 284.
33. Karler R, Turkanis SA: Cannabis and epilepsy. Adv Biosci 1978; 22-23: 619.
34. Feeney DM. Marijuana and epilepsy: paradoxical anticonvulsant and convulsant effects.
Adv Biosci 1978; 22-23: 643.
35. Feeney DM: Marijuana use among epileptics. JAMA 1976; 235: 1105.
36. Perez-Reyes M, Wingfield M: Cannabidiol and electroencephalographic epileptic activity.
JAMA 1974; 230: 1635.
37. Cunha JM, Carlini EA, Pereira AE, et al: Chronic administration of cannabidiol to
healthy volunteers and epileptic patients. Pharmacology 1980; 21: 175
Source: Marijuana Use And The Risk Of New Onset Seizures
