Species Strain Age Model type Disease model Method

Single compound or co-

administration
Cannabinoid doses
tested
Dose timing Route Effect
Gross effect
(proconvulsant =
RED,
anticonvulsant =
GREEN, no effect =
BLACK)
Notes Reference
10 mg/kg 5-135 mins before test stimulus
10 mg/kg 15-45 mins before test stimulus reduced number of
animals showing signs of seizures
1.25-10 mg/kg 15 mins before test stimulus 2.5-10 mg/kg reduced number of animals showing signs of seizures
10 mg/kg 15 -90 mins before priming stimulus
10 mg/kg 15-45 mins before priming stimulus showed reduced
signs of seizures
10-50 mg/kg 15 -90 mins after priming stimulus No effect
Mouse QS Adult Acute Generalised seizure PTZ 1-80 mg/kg 30 mins before testing No effect PTZ threshold model
30 mins before testing >160 mg/kg protected against hindlimb extension
30 mins before testing 20-75 mg/kg significantly increased hindlimb extension
20 mg/kg 30 mins before testing i.v. Significantly decreased hindlimb extension
THC plus CBD plus CBN
50 mg/kg THC, 50mg/kg
CBD, 50 mg/kg CBN
30 mins before testing p.o. Significantly decreased hindlimb extension
50mg/kg THC p.o. was proconvulsant alone and
50 mg/kg CBD nor CBN p.o. are anticonvulsant at
these doses
THC plus PHN
50mg/kg THC (with a
range on phenytoin
doses)
30 mins before testing p.o. Significantly reduced phenytoin ED50
A proconvulsant THC dose (50 mg/kg p.o.)
reduces AED ED50. Supports earlier proposal that
cannabis and phenytoin interact synergistically
(Loewe et al., 1947)
THC plus PHN plus CBD
50 mg/kg THC, 50 mg/kg
CBD (with a range of
phenytoin doses)
30 mins before testing p.o. Significantly reduced phenytoin ED50
AED ED50 further reduced from that achieved by
coadministration of THC with phenytoin
Mouse CF-1 Adult Acute Generalised seizure MES THC 1-100mg/kg 120 mins before testing i.p. Significant protection against seizures Blocked by SR141716A Wallace et al., 2001
THC plus PBL
25-50 mg/kg THC plus
9.3-40 mg/kg PBL
THC: 120 mins; PBL: 60 mins before
testing
THC: p.o.,
PBL: i.p.
Significant potentiation of PBL effect
Potentiation greater than that caused by CBD
reported in same study
THC plus CBD plus PBL
25 mg/kg THC, 25 mg/kg
CBD, 9.3-40 mg/kg
phenobarbitone
THC & CBD: 120 mins; PBL: 60 mins
before testing
THC &
CBD: p.o.,
PBL: i.p.
Significant potentiation of PBL effect
Potentiation comparable to that caused by co-
administration of THC 50 mg/kg alone
MES 15 mins to 24 hours before testing Significant increase in latency to hindlimb extension
Dose timing variation revealed peak effects at 30
mins
PTZ No effect
Nicotine No effect
Strychnine No effect
Single dose 50 mg/kg significantly dereased latency to seizure
o.d. for 6 days before testing No effect
0.25 mg/kg At onset of kindling Significant reduction of epileptiformafter-discharges
At stage 3 (head nodding)
At stage 5 (clonic jumping)
At kindling endpoint
Rat Sprague-Dawley Adult Chronic Temporal lobe epilepsy Pilocarpine-induced SRS 0.5-30mg/kg
Single dose immediately before EEG
and behavioural monitoring
i.p. Spontaneous seizures completely prevented Effect blocked by AM251 Wallace et al., 2003
Rat Not stated Adult Acute Generalised seizure PTZ 15-200 mg/kg 45 mins before testing i.p. Significant anticonvulsant effect Anticonvulsant effects described as 'unreliable'
Corcoran et al., 1973 &
Fried et al., 1973
Photogenic No effect
Amygdala kindling (electrical) Significant reduction in seizures and epileptiformafter-discharges
Photogenic
Significant anticonvulsant effect after treatment at 0.5 but not 2
hours
PTZ (35 mg/kg in epileptic
fowl)
PTZ (80 mg/kg in non-
epileptic fowl)
Mouse QS Adult Acute Generalised seizure MES CBD plus PBL
50 mg/kg CBD plus 9.3-
40 mg/kg
phenobarbitone
CBD: 2 hours, PBL: 1 hour before
testing
CBD: p.o.,
PBL: i.p.
Significant potentiation of PBL effect None Chesher et al., 1975
Mouse CF-1 Adult Acute Generalised seizure MES CBD 1-100mg/kg 120 mins before testing i.p. Significant protection against seizures Not blocked by SR141716A Wallace et al., 2001
Rat Not stated Adult Acute Generalised seizure MES 1.5-12 mg/kg 1 hour before testing i.p. Significant anticonvulsant effect Notably low dose required Izquierdo et al., 1973
Phytocannabinoids
D9-THC
Mouse
CBD
i.p.
Johnson et al., 1975
Wada et al., 1975
Wada et al., 1975
Loskota et al., 1975
Sofia et al., 1974
Karler et al., 1980
Chicken
None 30 mins before testing
Adult
Adult
Adult
Adult
Adult
Adult
Adult
Adult
Adult
Adult Karler et al., 1980 o.d. for 3-4 days before testing
Significant anticonvulsant effect
Acute Generalised seizure 0.25-1 mg/kg 0.5 or 2 hours before testing i.v.
100 mg/kg 6Hz electroshock
60Hz electroshock
THC
Gallus domesticus
Baboon Papio papio Chronic Generalised seizure 0.25-1 mg/kg
Cat
Gerbil
Boggan et al., 1973
Chesher et al., 1974
Chesher et al., 1975
THC
No effect
~60 minutes before testing
i.p.
Loss of proconvulsant effect upon latency with
chronic treatment suggests adaptation/tolerance
20 & 50 mg/kg
Standard MES model
Mouse Not stated Acute
Mouse QS Acute
Generalised seizure Acute Not stated
QS
Mouse Not stated Acute Generalised seizure
MES
No indication of tolerance after 3-4 days
repeated administration
100 mg/kg
Threshold to seizure reduced 60Hz electroshock
Not stated Chronic Generalised seizure Amygdala kindling (electrical) None
Increased threshold to seizure
Significantly decreased hindlimb extension
Significant anticonvulsant effect
None
0.25 - 4 mg/kg
Generalised seizure Chronic
Meriones
unguiculatus
6Hz electroshock
CBD
Generalised seizure
MES
No effect
i.p.
i.p.
Species exhibits photomyoclonus and is
susceptible to amygdala kindling
Subpopulation of chickens susceptible to photic
stimulation. Susceptible = 'epileptic'
No indication of tolerance after 3-4 days
repeated administration
up to 80 mg/kg
i.p. o.d. for 3-4 days before testing
i.p.
Significantly decreased hindlimb extension
Significant anticonvulsant effect
Published results of cannabinoid effects upon whole animal models of seizure and epilepsy
Generalised seizure i.p.
p.o.
Mouse C57BL/6 Acute
Model uses a priming stimulus at P+19 followed
by a test stimulus at P+28
25 - 200 mg/kg
Audiogenic priming
Generalised seizure MES
Acute Mouse Generalised seizure MES
Spontaneously epileptic
PTZ
MES
Mouse ICR Adult Acute Generalised seizure MES 120 mg/kg (ED50) 0.5-6 hours before testing i.p. Significant anticonvulsant effect None Karler et al., 1978
Rat Sprague-Dawley Adult Chronic Generalised seizure Limbic kindling (electrical) 0.3-3 mg/kg 15-300 minutes i.p. Significant increase in threshold to after-discharge None Turkanis et al., 1979
Rat Not stated Adult Chronic
Partial seizure with
secondary
generalisation
Cortical implantation of
cobalt
60 mg/kg Twice daily after implantation i.p. No effect None Colasanti et al., 1982
MES Significant anticonvulsant effect
3-mercaptoproprionic acid No effect
Picrotoxin Significant anticonvulsant effect
Isonicotinic acid Significant anticonvulsant effect
Bicuculline Significant anticonvulsant effect
Hydrazine Significant anticonvulsant effect
PTZ Significant anticonvulsant effect
Strychnine No effect
Rat Wistar-Kyoto Adult Acute Generalised seizure PTZ Significant anticonvulsant effects at 1 & 100 mg/kg None Jones et al., 2010
Rat Wistar-Kyoto Adult Acute Temporal lobe seizure Pilocarpine (acute) None Jones et al., 2012
Rat Wistar-Kyoto Adult Acute
Partial seizure with
secondary
generalisation
Penicillin None Jones et al., 2012
Mouse Adult Acute Generalised seizure MES CBN 230 mg/kg (ED50) 30 mins before testing i.p. Significant anticonvulsant effect None Karler et al., 1978
Rat Wistar-Kyoto Adult Acute Generalised seizure PTZ THCV 2.5 mg/kg 1 hour before testing i.p. Significant anticonvulsant effect Anticonvulsant effect lost Hill et al., 2010
Mouse DBA/2 Adult Acute Generalised seizure Audiogenic 1 hour before testing i.p. None
Mouse ICR Adult Acute Generalised seizure MES 1 hour before testing i.p. None
1 hour before testing i.p. None
3.5 hours before testing p.o. None
Acute Temporal lobe seizure Pilocarpine 1 hour before testing i.p. None
WIN55,212 plus clonazepam 15 mins before testing No effect
15mg/kg WIN55,212 significantly affects motor
function when co-administered (no effect noted
without WIN55,212)
WIN55,212 plus
ethosuximide
45 mins before testing
15mg/kg WIN55,212 enhanced anticonvulsant effect of
ethosuximide
15mg/kg WIN55,212 elevated ethosuximide brain
levels; 15mg/kg WIN55,212 significantly affects
motor function when co-administered (no effect
noted without WIN55,212)
WIN55,212 plus valproate 30 mins before testing 15mg/kg WIN55,212 enhanced anticonvulsant effect of valproate
15mg/kg WIN55,212 elevated valproate levels in
brain; 15mg/kg WIN55,212 significantly affects
motor function when co-administered (no effect
noted without WIN55,212)
WIN55,212 plus
phenobarbital
60 mins before testing
15mg/kg WIN55,212 enhanced anticonvulsant effect of
phenobarbitone
15mg/kg WIN55,212 significantly affects motor
function when co-administered (no effect noted
without WIN55,212)
WIN55,212 plus valproate 30 mins before testing 10mg/kg WIN55,212 enhanced anticonvulsant effect of valproate
10mg/kg and higher impaired motor function and
memory.
WIN55,212 plus
carbamazepine
30 mins before testing
10mg/kg WIN55,212 enhanced anticonvulsant effect of
carbamazepine
10mg/kg and higher impaired motor function.
WIN55,212 plus
phenobarbitone
60 mins before testing
10mg/kg WIN55,212 enhanced anticonvulsant effect of
phenobarbitone
10mg/kg and higher impaired motor function and
memory.
WIN55,212 plus phenytoin 120 mins before testing 10mg/kg WIN55,212 enhanced anticonvulsant effect of phenytoin
10mg/kg and higher impaired motor function and
memory.
WIN55,212 2.5-15mg/kg 20 mins before testing 15mg/kg elevated threshold to seizure 10mg/kg and higher impaired motor function.
Rat Wistar Juvenile (P20) Acute Generalised seizure Kainic acid WIN55,212 0.5-5mg/kg 90 mins before testing i.p.
All doses reduced severity vs vehicle controls but higher WIN
doses exerted a smaller effect on severity.
WIN effect on kainic acid induced seizures is
inversely related.
Rudenko, 2012
ACEA 1.25-15mg/kg i.p. Increased threshold to seizure
PMSF (FAAH inhibtor) used to prevent ACEA
metabolism
ACEA plus 30mg/kg
valproate
1.25-2.5mg/kg i.p. ACEA enhanced the anticonvulsant effect of valproate
ACEA increase available valproate concentration;
ACEA had not effect on motor function
Adult
Other phytocannabinoids
CB1 Agonists
Exogenous synthetic cannabinoids, endocannabinoids, derivatives and precursors
10 mins prior to testing Generalised seizure Acute Adult Swiss Mouse
Luszczki, 2011b
Adult
Adult
Adult
Adult
Luszczki, 2006 MES
10mg/kg and AED dose-
response
i.p.
MES Generalised seizure Acute
Swiss Mouse
5-15mg/kg Luszczki, 2011a Acute Generalised seizure PTZ
Chesher et al., 1974
Consroe et al., 1982
1, 10 & 100 mg/kg 1 hour before testing i.p.
Significant anticonvulsant effects at 1 mg/kg
CBDV 50-200 mg/kg Significant anticonvulsant effect
PTZ Generalised seizure
Mouse Not stated Acute Generalised seizure 50-200 mg/kg 30 mins before testing p.o.
Generalised seizure 5-400 mg/kg 60 minutes before testing i.p.
Apparently highly effective in models reliant
upon GABAergic systems.
CBD
No effect None
Acute
Rat Wistar-Kyoto
Hill et al., 2012 (submitted)
Mouse Not stated Acute
Rat Long-Evans Adult Acute Generalised seizure PTZ 40mg/kg 2 hours prior to testing
Animals did not exhibit tonic seizures but progressed directly to
clonic seizures
PEA did not affect any other seizure features.
Rat Long-Evans Adult Chronic Generalised seizure Amygdala kindling 1, 10 & 100mg/kg 2 hours prior to testing 1mg/kg PEA delayed onset of seizures
PEA only given prior to test session, not prior to
kindling stimuli. Effect on latency lost at 10 &
100mg/kg
PTZ Significantly reduced tonic convulsions
3-mercaptopropionic acid Significantly reduced tonic convulsions
Bicuculline Significantly reduced tonic convulsions
Strychnine Significantly reduced tonic convulsions
Picrotoxin Significantly reduced tonic convulsions
NMDA Significantly reduced tonic convulsions
MES 50 & 100mg/kg 50 & 100mg/kg significantly reduced seizures incidence Peak effect seen at 2 hours after administration
MES Anandamide 50mg/kg 50mg/kg significantly reduced seizures incidence
WIN55,212 0.5-4mg/kg Significant protection against seizures
WIN55,212 plus diazepam
0-4mg/kg of each in
mixed ratios
3:1 ratio (diazepam:WIN55,212) produced synergistic effect upon
protection from seizure
AM404 0.125-4mg/kg No significant effect
AM404 plus diazepam
0-4mg/kg of each in
mixed ratios
No significant effect
URB597 0.05-1mg/kg Significant protection against seizures
URB597 plus diazepam
0-2mg/kg of each in
mixed ratios
URB597 antagonised effects of diazepam URB597 is a FAAH inhibitor
WIN55,212 1-100ug Significant increase in latency to seizure
WIN55,212 plus isoguvacine
1-100ug and 5-50ug
respectively
No significant effect upon isoguvacine-induced increased latency
to seizure
Isoguvacine is a GABAAR agonist
URB597 10-100ug No significant effect
URB597 plus isoguvacine
10-100ug plus 5-50ug
respectively
No significant effect upon isoguvacine-induced increased latency
to seizure
Isoguvacine is a GABAAR agonist
URB602 10-500ug Significant increase in latency to seizure at all doses URB602 is a MAGL inhibitor
ACEA plus carbamazepine No significant effect
ACEA plus lamotrigine No significant effect
ACEA plus oxcarbazepine No significant effect
ACEA phenobarbitone Action of phenobarbitone significantly increased ACEA did not affect phenobarbitone availability
ACEA plus phenytoin No significant effect
ACEA plus topiramate No significant effect
Rat WAG/Rij Adult Chronic Absence Genetic WIN55,212 3-12mg/kg 2 hours prior to testing s.c.
Significantly decreased spike wave discharge incidence but
concomitant increase in duration
vanRijn, 2010
ACEA 0.25ug
45 mins after establishment of
epileptiformactivity.
i.c.v.
Frequency and amplitude of epileptiformactivity significantly
reduced
ACEA plus memantine
0.25ug and 1-20mg/kg
respectively
Memantine 30 mins and ACEA 45 mins
after establishment of epileptiform
activity.
i.c.v. Some potentiation of anticonvulsant effect of memantine Memantine is an NMDAR antagonist
Rat Wistar Adult Acute Partial seizure
Maximal dentate gyrus
activation
WIN55,212 1-21mg/kg
Monitored for up to 120 mins after
administration
i.p. Significant decrease in duration and increase in latency Blocked by co-administration of AM251 Rizzo, 2009
Rat Not stated Adult Acute Partial with secondary Penicillin (i.c.v.) ACEA 2.5-15ug Monitored for up to 120 mins after i.c.v. Significant decrease in frequency only at highest dose Blocked by co-administration of AM251 Kozan, 2009
ACEA 0.1-8mg/kg Up to 60 mins before testing i.p. Significant increase in threshold to seizure
ACEA plus naltrexone
0.1-8mg/kg and 1-
500pg/kg respectively
Up to 60 mins before testing i.p. Significant potentiation of ACEA anticonvulsant effect
Mouse NMRI Adult Acute Generalised seizure PTZ ACEA 0.1-4mg/kg 60 mins before testing i.p. Significant increase in seizure threshold at 2 & 4 mg/kg ACEA Effect blocked by AM251 Bahremand et al., 2009
Mouse NMRI Adult Acute Generalised seizure PTZ ACEA 0.1-8mg/kg 15 mins before testing i.p. Significant increase in threshold to seizure at 2-8mg/kg
Effect enhanced by ultra-low dose AM251
(100fg/kg-100ng/kg; fg = femtogram)
Gholizadeh, 2007
Mouse NMRI Adult Acute Generalised seizure PTZ ACPA 0.5-2mg/kg 60 mins before testing i.p. Significant increase in threshold to seizure at 1.5-2mg/kg Blocked by AM251 Shafaroodi et al., 2004
Rat Sprague-Dawley Adult Chronic Temporal lobe epilepsy Pilocarpine-induced SRS WIN55,212 5mg/kg
Single dose immediately before EEG
and behavioural monitoring
i.p. Spontaneous seizures completely prevented Effect blocked by AM251 Wallace et al., 2003
Mouse CF-1 Adult Acute Generalised seizure MES WIN55,212 1-100mg/kg 120 mins before testing i.p. Significant protection against seizures Blocked by SR141716A Wallace et al., 2001
30 or 60 mins before testing i.p. Seizure duration increased by 4mg/kg at 60 mins only Performed on fully kindled animals
30 mins before kindling stimulus i.p. Kindling significantly retarded Performed during kindling (epileptogenesis)
30 or 60 mins before testing i.p. 1 mg/kg at 30 mins increased afterdischarge threshold Performed on fully kindled animals
30 mins before kindling stimulus i.p. No significant effect Performed during kindling (epileptogenesis)
Rat Wistar Adult Acute Generalised seizure Audiogenic SR141716A 30mg/kg o.d. for 5 days p.o.
Seizure severity and duration increased in rats susceptible to
seizure.
Rats not susceptible to audiogenic seizure
showed no seizure response to SR141716A. High
rimonabant dose.
vanRijn, 2011a
AM251 0.25-5mg/kg No significant effect
AM251 plus diazepam
0-4mg/kg of each in
mixed ratios
No significant effect
Rat WAG/Rij Adult Chronic Absence Genetic AM251 6-12mg/kg 2 hours prior to testing s.c. No significant effect vanRijn, 2010
AM251 7.5ug
45 mins after establishment of
epileptiformactivity.
i.c.v.
Frequency and amplitude of epileptiformactivity significantly
increased
Cakil, 2011
AM251 plus memantine
7.5ug and 1-20mg/kg
respectively
Memantine 30 mins and AM251 45
mins after establishment of
epileptiformactivity.
i.c.v. No effect on anticonvulsant effect of memantine Memantine is an NMDAR antagonist
Rat Wistar Adult Acute Partial seizure
Maximal dentate gyrus
activation
AM251 1mg/kg
Monitored for up to 120 mins after
administration
i.p. No significant effect Rizzo, 2009
Rat Not stated Adult Acute
Partial with secondary
generalisation
Penicillin (i.c.v.) AM251 0.125-1ug
Monitored for up to 120 mins after
administration
i.c.v. Significant proconvulsant effect at 0.25 and 0.5ug only Kozan, 2009
Mouse NMRI Adult Acute Generalised seizure PTZ AM251 0.01-1mg/kg 15 mins before testing i.p. No significant effect Bahremand et al., 2009
Rat Sprague-Dawley Adult Chronic Epileptogenesis Kainic acid SR141716A 10mg/kg
Once at first sign of acute, kainic acid-
induced seizure
i.p. No effect Dudek, 2010
Naderi, 2011 Rat Wistar Adult Acute Generalised seizure PTZ
Mouse NMRI
30 mins before testing
5 mins before testing i.c.v.
Bahremand, 2008 Mouse NMRI Adult Acute Generalised seizure PTZ
2.5mg/kg 10 mins prior to testing i.p. Luszczki, 2010 Mouse Swiss Adult Acute Generalised seizure MES
Mouse
Acute
Partial with secondary
generalisation
Penicillin (i.c.v.) Rat Wistar Adult
NMRI Adult Acute Generalised seizure MES Naderi, 2008
Rat Wistar Adult Acute
Partial with secondary
generalisation
Penicillin (i.c.v.) Cakil, 2011
Wendt et al., 2011 Mouse NMRI Adult Chronic Generalised seizure Amygdala kindling
WIN55,212
URB597
2.5 & 4mg/kg
1 & 3mg/kg
Adult Acute Generalised seizure MES 30 mins before testing i.p. Naderi, 2008
Mouse OF1 Adult Acute Generalised seizure
Sheerin, 2004
N-palmitoylethanolamide
0.5 to 4 hours prior to testing
i.p.
i.p.
25mg/kg 2 hours prior to testing Ineffective against clonic convulsions
Lambert, 2001
Synthetic CB1 antagonists (see also THCV)
Rat Wistar Adult/Immature Chronic
Juvenile head trauma
followed by acute
proconvulsant
challenge 6 weeks later
Kainic acid SR141716A 1 & 10 mg/kg Immediately following head trama i.p.
SR141716A treatment reduced seizure susceptibility to control
levels
Echegoyen, 2009
Mouse NMRI Adult Acute Generalised seizure PTZ AM251 1fg/kg-1mg/kg 45 mins before testing i.p. No significant effect fg = femtogram(ultra-low dose) Gholizadeh, 2007
Mouse NMRI Adult Acute Generalised seizure PTZ AM251 0.5-3mg/kg 60 mins before testing i.p.
Significant proconvulsant effect at 0.75-3mg/kg (peak effect at
1mg/kg)
Shafaroodi et al., 2004
Rat Wistar Adult N/A None (healthy animals) EEG recording SR141716A 30mg/kg o.d. for at least 20 days p.o. 20% of animals (4/20) exhibited spontaneous seizures.
Note very high SR141716A dose; animals were
female and no note of stage of oeastrous cycle in
original report.
vanRijn, 2011a
THC 10mg/kg Increased incidence of seizures on handling
URB597 0.3mg/kg No effect on seizure incidence
HU210 0.01mg/kg Increased incidence of seizures on handling
o.d. for 8 weeks i.p. Dowie, 2010 Mouse R6/1 Adult Chronic Huntington's disease Behavioural observation
Notable effects in non-seizure models
Species Strain Age Model type Disease model Method
Single compound or co-
administration
Cannabinoid doses
tested
Dose timing Route Effect Gross effect Notes Reference
10 mg/kg 5-135 mins before test stimulus
10 mg/kg 15-45 mins before test stimulus reduced number of
animals showing signs of seizures
1.25-10 mg/kg 15 mins before test stimulus 2.5-10 mg/kg reduced number of animals showing signs of seizures
10 mg/kg 15 -90 mins before priming stimulus
10 mg/kg 15-45 mins before priming stimulus showed reduced
signs of seizures
10-50 mg/kg 15 -90 mins after priming stimulus No effect
Mouse QS Adult Acute Generalised seizure PTZ 1-80 mg/kg 30 mins before testing No effect PTZ threshold model
30 mins before testing >160 mg/kg protected against hindlimb extension
30 mins before testing 20-75 mg/kg significantly increased hindlimb extension
20 mg/kg 30 mins before testing i.v. Significantly decreased hindlimb extension
THC plus CBD plus CBN
50 mg/kg THC, 50mg/kg
CBD, 50 mg/kg CBN
30 mins before testing p.o. Significantly decreased hindlimb extension
50mg/kg THC p.o. was proconvulsant alone and
50 mg/kg CBD nor CBN p.o. are anticonvulsant at
these doses
THC plus PHN
50mg/kg THC (with a
range on phenytoin
doses)
30 mins before testing p.o. Significantly reduced phenytoin ED50
A proconvulsant THC dose (50 mg/kg p.o.)
reduces AED ED50. Supports earlier proposal that
cannabis and phenytoin interact synergistically
(Loewe et al., 1947)
THC plus PHN plus CBD
50 mg/kg THC, 50 mg/kg
CBD (with a range of
phenytoin doses)
30 mins before testing p.o. Significantly reduced phenytoin ED50
AED ED50 further reduced from that achieved by
coadministration of THC with phenytoin
Mouse CF-1 Adult Acute Generalised seizure MES THC 1-100mg/kg 120 mins before testing i.p. Significant protection against seizures Blocked by SR141716A Wallace et al., 2001
THC plus PBL
25-50 mg/kg THC plus
9.3-40 mg/kg PBL
THC: 120 mins; PBL: 60 mins before
testing
THC: p.o.,
PBL: i.p.
Significant potentiation of PBL effect
Potentiation greater than that caused by CBD
reported in same study
THC plus CBD plus PBL
25 mg/kg THC, 25 mg/kg
CBD, 9.3-40 mg/kg
phenobarbitone
THC & CBD: 120 mins; PBL: 60 mins
before testing
THC &
CBD: p.o.,
PBL: i.p.
Significant potentiation of PBL effect
Potentiation comparable to that caused by co-
administration of THC 50 mg/kg alone
MES 15 mins to 24 hours before testing Significant increase in latency to hindlimb extension
Dose timing variation revealed peak effects at 30
mins
PTZ No effect
Nicotine No effect
Strychnine No effect
Single dose 50 mg/kg significantly dereased latency to seizure
o.d. for 6 days before testing No effect
0.25 mg/kg At onset of kindling Significant reduction of epileptiform after-discharges
At stage 3 (head nodding)
At stage 5 (clonic jumping)
At kindling endpoint
Rat Sprague-Dawley Adult Chronic Temporal lobe epilepsy Pilocarpine-induced SRS 0.5-30mg/kg
Single dose immediately before EEG
and behavioural monitoring
i.p. Spontaneous seizures completely prevented Effect blocked by AM251 Wallace et al., 2003
Rat Not stated Adult Acute Generalised seizure PTZ 15-200 mg/kg 45 mins before testing i.p. Significant anticonvulsant effect Anticonvulsant effects described as 'unreliable'
Corcoran et al., 1973 &
Fried et al., 1973
Photogenic No effect
Amygdala kindling (electrical) Significant reduction in seizures and epileptiform after-discharges
Photogenic
Significant anticonvulsant effect after treatment at 0.5 but not 2
hours
PTZ (35 mg/kg in epileptic
fowl)
PTZ (80 mg/kg in non-
epileptic fowl)
Boggan et al., 1973
p.o.
Chesher et al., 1974
Mouse QS Adult Acute Generalised seizure MES
Mouse C57BL/6 Adult Acute Generalised seizure Audiogenic priming
THC
i.p.
25 - 200 mg/kg
Standard MES model
Mouse QS Adult Acute Generalised seizure MES
Model uses a priming stimulus at P+19 followed
by a test stimulus at P+28
Karler et al., 1980 6Hz electroshock Significant anticonvulsant effect
60Hz electroshock Threshold to seizure reduced
Chesher et al., 1975
Mouse Not stated Adult Acute Generalised seizure
MES
THC
100 mg/kg o.d. for 3-4 days before testing
None
Mouse Not stated Adult Acute Generalised seizure up to 80 mg/kg i.p.
i.p.
Significantly decreased hindlimb extension
No indication of tolerance after 3-4 days repeated
administration
Sofia et al., 1974
30 mins before testing None
Gerbil
Meriones
unguiculatus
Adult Chronic Generalised seizure Spontaneously epileptic 20 & 50 mg/kg i.p.
Loss of proconvulsant effect upon latency with
chronic treatment suggests adaptation/tolerance
Loskota et al., 1975
Cat Not stated Adult Chronic Generalised seizure Amygdala kindling (electrical) i.p.
Chicken Gallus domesticus Adult Acute Generalised seizure
None Wada et al., 1975
0.25 - 4 mg/kg No effect
Baboon Papio papio Adult Chronic Generalised seizure
0.25-1 mg/kg 0.5 or 2 hours before testing i.v.
Subpopulation of chickens susceptible to photic
stimulation. Susceptible = 'epileptic'
Johnson et al., 1975
No effect
0.25-1 mg/kg ~60 minutes before testing i.p.
Species exhibits photomyoclonus and is
susceptible to amygdala kindling
Wada et al., 1975
Species Strain Age Model type Disease model
Mouse QS Adult Acute Generalised seizure
Mouse CF-1 Adult Acute Generalised seizure
Rat Not stated Adult Acute Generalised seizure
Mouse ICR Adult Acute Generalised seizure
Rat Sprague-Dawley Adult Chronic Generalised seizure
Rat Not stated Adult Chronic
Partial seizure with
secondary
generalisation
Rat Wistar-Kyoto Adult Acute Generalised seizure
Rat Wistar-Kyoto Adult Acute Temporal lobe seizure
Rat Wistar-Kyoto Adult Acute
Partial seizure with
secondary
generalisation
Mouse Adult Acute Generalised seizure
Rat Wistar-Kyoto Adult Acute Generalised seizure
Mouse DBA/2 Adult Acute Generalised seizure
Mouse ICR Adult Acute Generalised seizure
Mouse Not stated Adult Acute Generalised seizure
Generalised seizure
Mouse Not stated Adult Acute Generalised seizure
Mouse Not stated Adult Acute
CBD
Other phytocannabinoids
Rat Wistar-Kyoto Adult
Acute Generalised seizure
Acute Temporal lobe seizure
Rat Wistar-Kyoto Adult
Method
Single compound or co-
administration
Cannabinoid doses
tested
MES CBD plus PBL
50 mg/kg CBD plus 9.3-
40 mg/kg
phenobarbitone
MES CBD 1-100mg/kg
MES 1.5-12 mg/kg
PTZ
MES
MES 120 mg/kg (ED50)
Limbic kindling (electrical) 0.3-3 mg/kg
Cortical implantation of
cobalt
60 mg/kg
MES
3-mercaptoproprionic acid
Picrotoxin
Isonicotinic acid
Bicuculline
Hydrazine
PTZ
Strychnine
PTZ
Pilocarpine (acute)
Penicillin
MES CBN 230 mg/kg (ED50)
PTZ THCV 2.5 mg/kg
Audiogenic
MES
MES
50-200 mg/kg
6Hz electroshock
60Hz electroshock
CBD
100 mg/kg
5-400 mg/kg
PTZ
CBD
Other phytocannabinoids
CBDV 50-200 mg/kg
1, 10 & 100 mg/kg
Pilocarpine
CBDV 50-200 mg/kg
Dose timing Route
CBD: 2 hours, PBL: 1 hour before
testing
CBD: p.o.,
PBL: i.p.
120 mins before testing i.p.
1 hour before testing i.p.
0.5-6 hours before testing i.p.
15-300 minutes i.p.
Twice daily after implantation i.p.
30 mins before testing i.p.
1 hour before testing i.p.
1 hour before testing i.p.
1 hour before testing i.p.
1 hour before testing i.p.
3.5 hours before testing p.o.
30 mins before testing p.o.
o.d. for 3-4 days before testing i.p.
i.p.
60 minutes before testing i.p.
CBD
Other phytocannabinoids
1 hour before testing
1 hour before testing i.p.
Effect Gross effect
Significant potentiation of PBL effect
Significant protection against seizures
Significant anticonvulsant effect
Significant anticonvulsant effect
Significant increase in threshold to after-discharge
No effect
Significant anticonvulsant effect
No effect
Significant anticonvulsant effect
Significant anticonvulsant effect
Significant anticonvulsant effect
Significant anticonvulsant effect
Significant anticonvulsant effect
No effect
Significant anticonvulsant effects at 1 & 100 mg/kg
Significant anticonvulsant effect
Significant anticonvulsant effect
No effect
Significant anticonvulsant effect
Significant anticonvulsant effect
Significantly decreased hindlimb extension
Significant anticonvulsant effects at 1 mg/kg
CBD
Other phytocannabinoids
Significant anticonvulsant effect
Significant anticonvulsant effect
Notes Reference
None Chesher et al., 1975
Not blocked by SR141716A Wallace et al., 2001
Notably low dose required Izquierdo et al., 1973
None Karler et al., 1978
None Turkanis et al., 1979
None Colasanti et al., 1982
None Jones et al., 2010
None Jones et al., 2012
None Jones et al., 2012
None Karler et al., 1978
Anticonvulsant effect lost Hill et al., 2010
None
None
None
None
No indication of tolerance after 3-4 days
repeated administration
Karler et al., 1980
Increased threshold to seizure
None Chesher et al., 1974
CBD
Other phytocannabinoids
Hill et al., 2012
Apparently highly effective in models reliant upon
GABAergic systems.
Consroe et al., 1982
None
Hill et al., 2012
Species Strain Age Model type Disease model
Rat Wistar Juvenile (P20) Acute Generalised seizure
Rat Long-Evans Adult Acute Generalised seizure
Rat Long-Evans Adult Chronic Generalised seizure
Mouse Swiss
Adult Acute Generalised seizure
Adult Acute Generalised seizure
Mouse Swiss Adult Acute Generalised seizure
Mouse OF1 Adult Acute Generalised seizure
Species Strain Age Model type Disease model
Rat WAG/Rij Adult Chronic Absence
Rat Wistar Adult Acute Partial seizure
Rat Not stated Adult Acute
Partial with secondary
generalisation
Mouse OF1 Adult Acute Generalised seizure
Rat Wistar Adult Acute Generalised seizure
Mouse NMRI Adult Acute Generalised seizure
Mouse Swiss Adult Acute Generalised seizure
Generalised seizure
Rat Wistar Adult Acute
Partial with secondary
generalisation
Mouse NMRI Adult Acute
Mouse NMRI Adult Acute Generalised seizure
Mouse NMRI Adult Acute Generalised seizure
Mouse NMRI Adult Acute Generalised seizure
Rat Sprague-Dawley Adult Chronic Temporal lobe epilepsy
Mouse CF-1 Adult Acute Generalised seizure
Mouse NMRI Adult Chronic Generalised seizure
Method
Single compound or co-
administration
Cannabinoid doses
tested
WIN55,212 plus clonazepam
WIN55,212 plus
ethosuximide
WIN55,212 plus valproate
WIN55,212 plus
phenobarbital
WIN55,212 plus valproate
WIN55,212 plus
carbamazepine
WIN55,212 plus
phenobarbitone
WIN55,212 plus phenytoin
WIN55,212 2.5-15mg/kg
Kainic acid WIN55,212 0.5-5mg/kg
ACEA 1.25-15mg/kg
ACEA plus 30mg/kg
valproate
1.25-2.5mg/kg
PTZ 40mg/kg
Amygdala kindling 1, 10 & 100mg/kg
PTZ
3-mercaptopropionic acid
Bicuculline
Strychnine
Picrotoxin
NMDA
MES
5-15mg/kg
MES
10mg/kg and AED dose-
response
PTZ
N-palmitoylethanolamide
25mg/kg
MES 50 & 100mg/kg
MES Anandamide 50mg/kg
WIN55,212 0.5-4mg/kg
WIN55,212 plus diazepam
0-4mg/kg of each in
mixed ratios
AM404 0.125-4mg/kg
AM404 plus diazepam
0-4mg/kg of each in
mixed ratios
URB597 0.05-1mg/kg
URB597 plus diazepam
0-2mg/kg of each in
mixed ratios
Method
Single compound or co-
administration
Cannabinoid doses
tested
WIN55,212 1-100ug
WIN55,212 plus isoguvacine
1-100ug and 5-50ug
respectively
URB597 10-100ug
URB597 plus isoguvacine
10-100ug plus 5-50ug
respectively
URB602 10-500ug
ACEA plus carbamazepine
ACEA plus lamotrigine
ACEA plus oxcarbazepine
ACEA phenobarbitone
ACEA plus phenytoin
ACEA plus topiramate
Genetic WIN55,212 3-12mg/kg
ACEA 0.25ug
ACEA plus memantine
0.25ug and 1-20mg/kg
respectively
Maximal dentate gyrus
activation
WIN55,212 1-21mg/kg
Penicillin (i.c.v.) ACEA 2.5-15ug
ACEA 0.1-8mg/kg
ACEA plus naltrexone
0.1-8mg/kg and 1-
500pg/kg respectively
N-palmitoylethanolamide
PTZ
MES
MES 2.5mg/kg
PTZ
Penicillin (i.c.v.)
PTZ ACEA 0.1-4mg/kg
PTZ ACEA 0.1-8mg/kg
PTZ ACPA 0.5-2mg/kg
Pilocarpine-induced SRS WIN55,212 5mg/kg
MES WIN55,212 1-100mg/kg
URB597 1 & 3mg/kg
Amygdala kindling
WIN55,212 2.5 & 4mg/kg
Dose timing Route
15 mins before testing
45 mins before testing
30 mins before testing
60 mins before testing
30 mins before testing
30 mins before testing
60 mins before testing
120 mins before testing
20 mins before testing
90 mins before testing i.p.
i.p.
i.p.
2 hours prior to testing
2 hours prior to testing
i.p.
10 mins prior to testing
i.p.
2 hours prior to testing
i.p.
Dose timing Route
2 hours prior to testing s.c.
45 mins after establishment of
epileptiform activity.
i.c.v.
Memantine 30 mins and ACEA 45 mins
after establishment of epileptiform
activity.
i.c.v.
Monitored for up to 120 mins after
administration
i.p.
Monitored for up to 120 mins after
administration
i.c.v.
Up to 60 mins before testing i.p.
Up to 60 mins before testing i.p.
i.p.
0.5 to 4 hours prior to testing
30 mins before testing i.p.
5 mins before testing i.c.v.
10 mins prior to testing i.p.
60 mins before testing i.p.
15 mins before testing i.p.
60 mins before testing i.p.
Single dose immediately before EEG
and behavioural monitoring
i.p.
120 mins before testing i.p.
30 or 60 mins before testing i.p.
30 mins before kindling stimulus i.p.
30 or 60 mins before testing i.p.
30 mins before kindling stimulus i.p.
Effect Gross effect
No effect
15mg/kg WIN55,212 enhanced anticonvulsant effect of
ethosuximide
15mg/kg WIN55,212 enhanced anticonvulsant effect of valproate
15mg/kg WIN55,212 enhanced anticonvulsant effect of
phenobarbitone
10mg/kg WIN55,212 enhanced anticonvulsant effect of valproate
10mg/kg WIN55,212 enhanced anticonvulsant effect of
carbamazepine
10mg/kg WIN55,212 enhanced anticonvulsant effect of
phenobarbitone
10mg/kg WIN55,212 enhanced anticonvulsant effect of phenytoin
15mg/kg elevated threshold to seizure
All doses reduced severity vs vehicle controls but higher WIN doses
exerted a smaller effect on severity.
Increased threshold to seizure
ACEA enhanced the anticonvulsant effect of valproate
Animals did not exhibit tonic seizures but progressed directly to
clonic seizures
1mg/kg PEA delayed onset of seizures
Significantly reduced tonic convulsions
Significantly reduced tonic convulsions
Significantly reduced tonic convulsions
Significantly reduced tonic convulsions
Significantly reduced tonic convulsions
Significantly reduced tonic convulsions
50 & 100mg/kg significantly reduced seizures incidence
50mg/kg significantly reduced seizures incidence
Significant protection against seizures
3:1 ratio (diazepam:WIN55,212) produced synergistic effect upon
protection from seizure
No significant effect
No significant effect
Significant protection against seizures
URB597 antagonised effects of diazepam
Effect Gross effect
Significant increase in latency to seizure
No significant effect upon isoguvacine-induced increased latency to
seizure
No significant effect
No significant effect upon isoguvacine-induced increased latency to
seizure
Significant increase in latency to seizure at all doses
No significant effect
No significant effect
No significant effect
Action of phenobarbitone significantly increased
No significant effect
No significant effect
Significantly decreased spike wave discharge incidence but
concomitant increase in duration
Frequency and amplitude of epileptiform activity significantly
reduced
Some potentiation of anticonvulsant effect of memantine
Significant decrease in duration and increase in latency
Significant decrease in frequency only at highest dose
Significant increase in threshold to seizure
Significant potentiation of ACEA anticonvulsant effect
Significant increase in seizure threshold at 2 & 4 mg/kg ACEA
Significant increase in threshold to seizure at 2-8mg/kg
Significant increase in threshold to seizure at 1.5-2mg/kg
Spontaneous seizures completely prevented
Significant protection against seizures
Seizure duration increased by 4mg/kg at 60 mins only
Kindling significantly retarded
1 mg/kg at 30 mins increased afterdischarge threshold
No significant effect
Notes Reference
15mg/kg WIN55,212 significantly affects motor
function when co-administered (no effect noted
without WIN55,212)
15mg/kg WIN55,212 elevated ethosuximide brain
levels; 15mg/kg WIN55,212 significantly affects
motor function when co-administered (no effect
noted without WIN55,212)
15mg/kg WIN55,212 elevated valproate levels in
brain; 15mg/kg WIN55,212 significantly affects
motor function when co-administered (no effect
noted without WIN55,212)
15mg/kg WIN55,212 significantly affects motor
function when co-administered (no effect noted
without WIN55,212)
10mg/kg and higher impaired motor function and
memory.
10mg/kg and higher impaired motor function.
10mg/kg and higher impaired motor function and
memory.
10mg/kg and higher impaired motor function and
memory.
10mg/kg and higher impaired motor function.
WIN effect on kainic acid induced seizures is
inversely related.
Rudenko, 2012
PMSF (FAAH inhibtor) used to prevent ACEA
metabolism
ACEA increase available valproate concentration;
ACEA had not effect on motor function
PEA did not affect any other seizure features.
PEA only given prior to test session, not prior to
kindling stimuli. Effect on latency lost at 10 &
100mg/kg
Luszczki, 2011a
Luszczki, 2011b
Luszczki, 2006
Sheerin, 2004
Ineffective against clonic convulsions
Lambert, 2001
Peak effect seen at 2 hours after administration
URB597 is a FAAH inhibitor
Notes Reference
Isoguvacine is a GABAAR agonist
Isoguvacine is a GABAAR agonist
URB602 is a MAGL inhibitor
ACEA did not affect phenobarbitone availability
vanRijn, 2010
Memantine is an NMDAR antagonist
Blocked by co-administration of AM251 Rizzo, 2009
Blocked by co-administration of AM251 Kozan, 2009
Lambert, 2001
Naderi, 2008
Naderi, 2011
Luszczki, 2010
Cakil, 2011
Bahremand, 2008
Effect blocked by AM251 Bahremand et al., 2009
Effect enhanced by ultra-low dose AM251
(100fg/kg-100ng/kg; fg = femtogram)
Gholizadeh, 2007
Blocked by AM251 Shafaroodi et al., 2004
Effect blocked by AM251 Wallace et al., 2003
Blocked by SR141716A Wallace et al., 2001
Performed on fully kindled animals
Performed during kindling (epileptogenesis)
Performed on fully kindled animals
Performed during kindling (epileptogenesis)
Wendt et al., 2011
Species Strain Age Model type Disease model
Rat Wistar Adult Acute Generalised seizure
Rat WAG/Rij Adult Chronic Absence
Rat Wistar Adult Acute Partial seizure
Rat Not stated Adult Acute
Partial with secondary
generalisation
Mouse NMRI Adult Acute Generalised seizure
Rat Sprague-Dawley Adult Chronic Epileptogenesis
Rat Wistar Adult/Immature Chronic
Juvenile head trauma
followed by acute
proconvulsant
challenge 6 weeks later
Mouse NMRI Adult Acute Generalised seizure
Mouse NMRI Adult Acute Generalised seizure
Rat Wistar Adult Acute
Partial with secondary
generalisation
Mouse NMRI Adult Acute Generalised seizure
Method
Single compound or co-
administration
Cannabinoid doses
tested
Audiogenic SR141716A 30mg/kg
AM251 0.25-5mg/kg
AM251 plus diazepam
0-4mg/kg of each in
mixed ratios
Genetic AM251 6-12mg/kg
AM251 7.5ug
AM251 plus memantine
7.5ug and 1-20mg/kg
respectively
Maximal dentate gyrus
activation
AM251 1mg/kg
Penicillin (i.c.v.) AM251 0.125-1ug
PTZ AM251 0.01-1mg/kg
Kainic acid SR141716A 10mg/kg
Kainic acid SR141716A 1 & 10 mg/kg
PTZ AM251 1fg/kg-1mg/kg
PTZ AM251 0.5-3mg/kg
Penicillin (i.c.v.)
MES
Dose timing Route
o.d. for 5 days p.o.
2 hours prior to testing s.c.
45 mins after establishment of
epileptiform activity.
i.c.v.
Memantine 30 mins and AM251 45
mins after establishment of
epileptiform activity.
i.c.v.
Monitored for up to 120 mins after
administration
i.p.
Monitored for up to 120 mins after
administration
i.c.v.
15 mins before testing i.p.
Once at first sign of acute, kainic acid-
induced seizure
i.p.
Immediately following head trama i.p.
45 mins before testing i.p.
60 mins before testing i.p.
30 mins before testing
Effect Gross effect
Seizure severity and duration increased in rats susceptible to
seizure.
No significant effect
No significant effect
No significant effect
Frequency and amplitude of epileptiform activity significantly
increased
No effect on anticonvulsant effect of memantine
No significant effect
Significant proconvulsant effect at 0.25 and 0.5ug only
No significant effect
No effect
SR141716A treatment reduced seizure susceptibility to control
levels
No significant effect
Significant proconvulsant effect at 0.75-3mg/kg (peak effect at
1mg/kg)
Notes Reference
Rats not susceptible to audiogenic seizure
showed no seizure response to SR141716A. High
rimonabant dose.
vanRijn, 2011a
vanRijn, 2010
Cakil, 2011
Memantine is an NMDAR antagonist
Rizzo, 2009
Kozan, 2009
Bahremand et al., 2009
Dudek, 2010
Echegoyen, 2009
fg = femtogram (ultra-low dose) Gholizadeh, 2007
Shafaroodi et al., 2004
Naderi, 2008