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Phytocannabinoids as novel therapeutic agents in CNS disorders

By Andrew J. Hill, Claire M. Williams, Benjamin J. Whalley and Gary J. Stephens

Abstract

The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB1 receptors by the major pCB, Δ9-tetrahydrocannabinol (Δ9-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ9-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard,\ud research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ9tetrahydrocannabivarin (Δ9-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ9-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ9-THC pCB-based medicines

Publisher: Elsevier
Year: 2012
OAI identifier: oai:centaur.reading.ac.uk:24227

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Citations

  1. (2002). (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. doi
  2. (1995). 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.
  3. (1973). 9 -Tetrahydrocannabinol effect on audiogenic seizure susceptibility.
  4. (1973). 9 -Tetrahydrocannabinol in depressed patients.
  5. (2003). A cannabichromene (CBC) extract alters behavioral despair on the mouse tail suspension test of depression.
  6. (2006). A cannabigerol (CBC) extract alters behavioral dispair in an animal model of depression.
  7. (1983). A double-blind trial of 9-THC in primary anorexia nervosa.
  8. (2010). A low-Delta9tetrahydrocannabinol cannabis extract induces hyperphagia in rats. Behav Pharmacol.
  9. (1888). A manual of diseases of the nervous system.
  10. (2006). A molecular link between the active component of marijuana and Alzheimer's disease pathology.
  11. (2004). A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.
  12. (2009). A pilot study using nabilone for symptomatic treatment in Huntington's disease.
  13. (2003). A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.
  14. (2011). A randomized, double-blind, placebo-controlled, crossover study to evaluate the abuse potential of nabiximols oromucosal spray in subjects with a history of recreational cannabis use.
  15. (2011). A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex((R)) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis.
  16. (2006). A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol.
  17. (2010). AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.
  18. (1982). Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. doi
  19. (2001). Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity.
  20. (2008). Affect dysregulation in cannabis abusers: a study in adolescents and young adults. doi
  21. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors.
  22. Allosteric modulation of the cannabinoid CB1 receptor. doi
  23. (1974). An archaeological and historical account of cannabis in China. doi
  24. (1979). An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats.
  25. (1993). Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction.
  26. (1995). Anandamide, an endogenous cannabinomimetic eicosanoid: 'killing two birds with one stone'. doi
  27. (1997). Animal models of intractable epilepsy. doi
  28. (2007). Anorexia of aging in long term care: is dronabinol an effective appetite stimulant?--a pilot study.
  29. (1990). Antianxiety effect of cannabidiol in the elevated plus-maze.
  30. (1974). Anticonvulsant activity of delta9-tetrahydrocannabilol and its 11-hydroxy and 8alpha, 11-dihydroxy metabolites in the frog.
  31. (1986). Anticonvulsant effect of cannabidiol.
  32. (2010). Anticonvulsant effects of GWP42006 in vitro and in vivo in rat. Physiology
  33. (1974). Anticonvulsant properties of cannabidiol.
  34. (1974). Anticonvulsant properties of delta 9-tetrahydrocannabinol and other cannabinoids.
  35. (2010). Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.
  36. (2010). Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors.
  37. (1949). Antiepileptic action of marijuana-active substances. Federation Proceedings,
  38. (2006). Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. doi
  39. (2001). Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects.
  40. (2010). Association between psychopathology and substance use among school-going adolescents in Cape Town, South Africa.
  41. (1973). Barbiturate-induced transmitter release at a frog neuromuscular junction.
  42. (1986). Behavioral analysis of marijuana effects on food intake in humans.
  43. (2010). Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington's disease transgenic mice. doi
  44. (2010). Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation.
  45. (2009). Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation.
  46. (1998). Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. doi
  47. (2011). Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimers' disease. Mol Pharmacol.
  48. (2010). Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.
  49. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro.
  50. (2009). Cannabidiol for the treatment of psychosis in Parkinson's disease. doi
  51. (1986). Cannabidiol in dystonic movement disorders.
  52. Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL1beta and iNOS expression.
  53. (2006). Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NFkappaB involvement.
  54. (2011). Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways.
  55. (2007). Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors.
  56. (2011). Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study.
  57. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients.
  58. (2009). Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.
  59. (2009). Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels.
  60. (2010). Cannabidiol was ineffective for manic episode of bipolar affective disorder. doi
  61. (2006). Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. doi
  62. (2001). Cannabinoid CB(1) receptor agonists produce cerebellar dysfunction in mice.
  63. (2004). Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study.
  64. (2003). Cannabinoid influences on palatability: microstructural analysis of sucrose drinking after delta(9)-tetrahydrocannabinol, anandamide, 2-arachidonoyl glycerol and SR141716.
  65. (2009). Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus. doi
  66. (2001). Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates.
  67. (1990). Cannabinoid receptor localization in brain.
  68. (2006). Cannabinoid signalling. doi
  69. (2001). Cannabinoid-induced motor incoordination through the cerebellar CB(1) receptor in mice. doi
  70. (2000). Cannabinoids control spasticity and tremor in a multiple sclerosis model.
  71. (2010). Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells. doi
  72. (2009). Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev,
  73. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. doi
  74. (2005). Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. doi
  75. (2005). Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. doi
  76. (2009). Cannabis and anxiety: a critical review of the evidence.
  77. (2010). Cannabis constituents modulate delta9-tetrahydrocannabinol-induced hyperphagia in rats.
  78. (1856). Cannabis indica in convulsions.
  79. (2011). Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation.
  80. (2010). Cannabis-based medicines in multiple sclerosis--a review of clinical studies.
  81. (1990). Case report: the effect of tetrahydrocannabinol on food intake during chemotherapy.
  82. (2005). CB1 cannabinoid receptor-mediated modulation of food intake in mice.
  83. (2008). CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies.
  84. (1982). Central excitatory properties of delta 9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats.
  85. (2001). Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolase.
  86. (1998). Characterization of cytochrome P450 3A inactivation by cannabidiol: possible involvement of cannabidiol-hydroxyquinone as a P450 inactivator.
  87. (1970). Chemical basis of hashish activity.
  88. (2005). Chemical constituents of marijuana: the complex mixture of natural cannabinoids.
  89. (2005). Cholinesterase inhibitors in the treatment of dementia.
  90. (1997). Clinical experience with nabilone for chronic pain.
  91. (2006). Comparison of the effects of cannabidiol in two mouse models of depression.
  92. (1983). Convulsant-anticonvulsant properties of delta-9-tetrahydrocannabinol in rabbits.
  93. (2006). Decreased depression in marijuana users. doi
  94. (1989). Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis.
  95. (2006). Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.
  96. (2010). Delta-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. doi
  97. (2007). Delta9-tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors.
  98. (2007). Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity.
  99. (1987). Different cannabinoids exhibit different electrophysiological properties.
  100. (1991). Differential effects of delta-9-tetrahydrocannabinol and its 11-hydroxy metabolite on sodium current in neuroblastoma cells.
  101. (2007). Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
  102. (2009). Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.
  103. (2008). Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug Alcohol Depend,
  104. (2004). Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.
  105. (2009). Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis.
  106. (2004). Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial.
  107. (1990). Double-blind clinical study of cannabidiol as a secondary anticonvulsant.
  108. (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.
  109. (1997). Dronabinol may help behaviour problems in Alzheimers disease.
  110. (2004). Drug Administration
  111. (1997). Early onset cannabis use and psychosocial adjustment in young adults.
  112. (1993). Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers.
  113. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow.
  114. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.
  115. (2008). Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes.
  116. (2006). Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease.
  117. (1988). Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory.
  118. (2011). Effects of the Allosteric Antagonist 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 Receptor Modulation in the Cerebellum.
  119. (2001). Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial selfstimulation in Lewis rats.
  120. (1983). Effects on variable-interval performance in rats of delta 9-tetrahydrocannabinol and cannabidiol, separately and in combination.
  121. (2004). Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.
  122. (1981). Electrophysiologic properties of the cannabinoids.
  123. (2008). Endocannabinoids and the neurochemistry of gluttony.
  124. (2003). Endogenous cannabinoid system as a modulator of food intake.
  125. (2008). Enhanced striatal glutamate release after the administration of rimonabant to 6-hydroxydopamine-lesioned rats.
  126. (2010). Epilepsy in the elderly. doi
  127. (2007). Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties.
  128. (2005). Evidence that the plant cannabinoid Delta(9)-tetrahydrocannabivarin is a cannabinoid CB(1) and CB(2) receptor antagonist.
  129. (1981). Excitatory and depressant effects of delta 9-tetrahydrocannabinol and cannabidiol on cortical evoked responses in the conscious rat.
  130. (2007). Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation. doi
  131. (2008). Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats.
  132. (2010). GPR55, a lysophosphatidylinositol receptor with cannabinoid sensitivity? doi
  133. (2007). GPR55: a new member of the cannabinoid receptor clan?
  134. (2007). History of cannabis and its preparations in saga, science, and sobriquet.
  135. (2004). Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors.
  136. (1971). Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine.
  137. (2010). Huntington's disease: pathogenesis to animal models. doi
  138. (1998). Hyperphagia in pre-fed rats following oral delta9-THC.
  139. (2005). Identification and functional characterization of brainstem cannabinoid CB2 receptors.
  140. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
  141. (1990). Illicit drug use and the risk of newonset seizures.
  142. (1998). Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.
  143. (2008). Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain.
  144. (2003). Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212.
  145. (1999). Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist.
  146. (2010). Inflammation and Alzheimer's disease. doi
  147. (1975). Influence of anticonvulsant cannabinoids on posttetanic potentiation at isolated bullfrog ganglia.
  148. (1977). Influence of delta9-tetrahydrocannabinol and cannabidiol on photically evoked after-discharge potentials.
  149. (1996). Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids.
  150. (2008). Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol.
  151. (2001). Investigator Brochure - Cannabis based medicine extract sublingual formulations.
  152. (2001). Involvement of the cerebellar adenosine A(1) receptor in cannabinoid-induced motor incoordination in the acute and tolerant state in mice. doi
  153. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. doi
  154. (2010). Lack of positive allosteric modulation of mutated alpha(1)S267I glycine receptors by cannabinoids.
  155. (2006). Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis.
  156. (2010). Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson's disease in the rat.
  157. (2011). Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.
  158. (2006). Malnutrition in ageing. doi
  159. (1997). Marihuana, the forbidden medicine,
  160. (2004). Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center.
  161. (2007). Marijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature.
  162. (2008). Mechanisms of neurodegeneration in Huntington's disease.
  163. (2008). Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. doi
  164. (2001). Medical use of cannabis: experience in
  165. Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?
  166. (2001). Medicinal use of cannabis: history and current status.
  167. (2010). Microglial activation and chronic neurodegeneration. doi
  168. (1993). Molecular characterization of a peripheral receptor for cannabinoids. doi
  169. (1996). Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides.
  170. (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide.
  171. (1995). Nabilone in the treatment of multiple sclerosis. doi
  172. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.
  173. (2008). Neuroanatomic comparison of bipolar adolescents with and without cannabis use disorders.
  174. (2010). Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease.
  175. (2010). Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy. doi
  176. (2010). Neuropathology of Alzheimer's disease.
  177. (2001). Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.
  178. (2010). Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity in experimental autoimmune encephalomyelitis. doi
  179. (2003). Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in Nmethyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.
  180. (2011). Neuroprotective strategies involving ROS in Alzheimer disease. doi
  181. (2001). Nutritional management of individuals with Alzheimer‟s disease and other progressive dementias. doi
  182. (2002). Observational analysis of feeding induced by Delta9-THC and anandamide.
  183. (2004). On the application of cannabis in paediatrics and epileptology.
  184. On the preparations of the Indian hemp, or gunjah (Cannabis indica).
  185. (2004). On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.
  186. (2007). Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.
  187. (2001). Pharmacology and effects of cannabis: a brief review.
  188. (2005). Plant cannabinoids: a neglected pharmacological treasure trove.
  189. (2008). Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. doi
  190. (2010). Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from
  191. (2004). Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo. doi
  192. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.
  193. (2002). Rates of psychiatric comorbidity among U.S. residents with lifetime cannabis dependence.
  194. (1991). Recent clinical experience with dronabinol. doi
  195. (2006). Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids.
  196. (2002). Reflections on nutritional issues associated with cancer therapy.
  197. (1860). Report of the Ohio State Medical Committee on Cannabis indica,
  198. (2002). Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine.
  199. (2005). Sativex for the management of multiple sclerosis symptoms.
  200. (1997). Seizure Disorders,
  201. (2009). Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model. doi
  202. (2001). SR141716, a CB1 receptor antagonist, decreases the sensitivity to the reinforcing effects of electrical brain stimulation in rats. doi
  203. (2005). Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation.
  204. (2002). Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease.
  205. (2005). Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops. doi
  206. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. doi
  207. (1987). Structureanticonvulsant activity relationships of cannabidiol analogs.
  208. (1980). Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice.
  209. (2011). Supply and demand for endocannabinoids.
  210. (2004). Survey on cannabis use in Parkinson's disease: Subjective improvement of motor symptoms.
  211. (2003). Survey on the medical use of cannabis and THC in Germany.
  212. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in animal models of Parkinson's disease.
  213. (2009). Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice.
  214. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.
  215. (2008). Targeting the endocannabinoid system: to enhance or reduce?
  216. (1973). The anticonvulsant activity of cannabidiol and cannabinol.
  217. (1976). The antiepileptic potential of the cannabinoids,
  218. (2005). The biosynthesis, fate and pharmacological properties of endocannabinoids. Handb Exp Pharmacol,
  219. (1981). The cannabinoids as potential antiepileptics.
  220. (2009). The CB(1) antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson's disease.
  221. (2009). The current status and future perspectives of studies of cannabinoid receptor 1 antagonists as anti-obesity agents. doi
  222. (2010). The development of cannabinoid CBII receptor agonists for the treatment of central neuropathies.
  223. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.
  224. (2009). The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.
  225. (2006). The emerging role of the endocannabinoid system in endocrine regulation and energy balance.
  226. (2010). The endocannabinoid system and psychiatric disorders.
  227. (2006). The endocannabinoid system controls key epileptogenic circuits in the hippocampus. doi
  228. (2009). The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. doi
  229. (2009). The enigmatic pharmacology of GPR55.
  230. (2003). The inheritance of chemical phenotype in Cannabis sativa L.
  231. (2011). The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. doi
  232. (1971). The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish.
  233. (2002). The legalization of Cannabis for medical use.
  234. (1999). The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716.
  235. (2010). The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptormediated currents in Xenopus laevis oocytes. doi
  236. (2009). The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
  237. (1986). The pharmacohistory of Cannabis sativa,
  238. (2008). The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum.
  239. (2010). The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice.
  240. the presence and functional expression of cannabinoid CB2 receptors in brain.
  241. (1981). The religious and medicinal uses of Cannabis in China, India and Tibet.
  242. (1981). The seed and the soil: effect of dosage, personality and starting state on the response to delta 9 tetrahydrocannabinol in man.
  243. (2009). The spinocerebellar ataxias.
  244. (2009). The therapeutic potential of novel cannabinoid receptors.
  245. (2001). The therapeutic use of Cannabis sativa L. in Arabic medicine. doi
  246. Therapeutic action of cannabinoids in a murine model of multiple sclerosis.
  247. (2001). Therapeutic aspects of cannabis and cannabinoids.
  248. (2008). Therapeutic effects of Delta9-THC and modafinil in a marmoset Parkinson model.
  249. (1997). Therapeutic uses of cannabis.
  250. Therapeutical uses and toxic effects of Cannabis indica.
  251. (1978). Tolerance to delta9-tetrahydrocannabinol in adapted and nonadapted rabbits. doi
  252. (2009). Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. doi

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