Therapeutic Uses of Cannabis B. Brands, Ph.D. Centre for Addiction and Mental Health Clinical Research Department Department of Pharmacology University of Toronto (Presented by Wende Wood, B.A., B.S.P., B.C.P.P. Drug Information and Drug Use Evaluation Pharmacist)
Therapeutic Uses of Cannabis. B. Brands, Ph.D. Centre for Addiction and Mental Health Clinical Research Department Department of Pharmacology University of Toronto (Presented by Wende Wood, B.A., B.S.P., B.C.P.P. Drug Information and Drug Use Evaluation Pharmacist). - PowerPoint PPT Presentation
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Therapeutic Uses of Cannabis
B. Brands, Ph.D.Centre for Addiction and Mental Health
Clinical Research Department
Department of Pharmacology
University of Toronto
(Presented by Wende Wood, B.A., B.S.P., B.C.P.P.
Drug Information and Drug Use Evaluation Pharmacist)
Excerpted from: Kalant, H. (2001) Medicinal use of cannabis: History and current status. Pain Res. Manage 6(2): 80-91.
Other Sources: Baker et al (2003) The therapeutic potential of cannabis. The Lancet. Neurology 2: 291-298.
Croxford, J.L. (2003) Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 17(3): 179-202.
Joy, J.E. et al (1999) Marijuana and medicine: Assessing the science base. Washington, D.C., National Academy Press.
Additional Reading: Bagshaw, S.M. (2002) Medical efficacy ofcannabinoids and marijuana: A comprehensive review of the literature. Journal of Palliative Care 18(2) 111-122.
Iverson, L. (2003) Cannabis and the Brain. Brain 126: 1252-1270.
Kalant, 2001
Mechanisms of Action
Mechanisms of Action (cont’d)
Location of Cannabinoid ReceptorsLocation Structure Function
CB1 receptors
CNS Hippocampus Memory storage
Cerebellum Coordination of motor function, posture, balance
Periphery Lymphoid organs Cell-mediated and innate immunity
Vascular smooth muscle cells Control of blood pressure
Duodenum, ileum, myenteric plexus Control of emesis
Lung smooth muscle cells Bronchodilation
Eye ciliary body Intraocular pressure
CB2 receptors
Periphery Lymphoid tissue Cell-mediated and innate immunity
Peripheral nerve terminals Peripheral nervous system
Retina Intraocular pressure
CNS Cerebellar granule cells mRNA Coordination of motor function
Croxford, JL. CNS Drugs 2003; 17(3)
Baker et al, 2003
• receptors are linked to Gi protein
– decrease adenylyl cyclase activity
– prevent activation of various Ca2+ channels and activate K+ influx
– major effect - decreased cell excitability
– probably modify responses to various neurotransmitters, and NT release
Diagram of Neuron with Synapse
Individual nerve cells, or neurons, both send and receive cellular signals to and from neighbouring neurons, but for the purposes of the previous diagram, only one activity is indicated for each cell. Neurotransmitter molecules are released from the neuron terminal and move across the gap between the ‘sending’ and ‘receiving’ neurons. A signal is transmitted to the receiving neuron when the neurotransmitters have bound to the receptor on its surface.
From: Marijuana and Medicine: Assessing the Science Base, IOM 1999
Relative Affinities of Various Cannabinoids for CB1 and CB2 Cannabinoid Receptors
Kalant, 2001
Possible Routes of Administration
Possible Routes of Administration (cont’d)
• IV - very low water solubility, requires special formulation
• receptors in periaqueductal gray mainly (direct local injection effective)
• separate from opioid analgesia mechanism– naloxone blocks morphine analgesia but not THC
analgesia– CB1 blocker (SR 141716A) blocks THC but not
morphine analgesia
• but THC and morphine augment each other’s effects - possibility of combined use
Analgesia (cont’d)
• both oral THC and smoked marijuana work– onset of action faster with smoking– for chronic pain, speed not necessary
• new water-soluble esters of THC-acid analogs– analgesic and anti-inflammatory action– no psychoactivity, no gastric irritation– possible replacement for NSAIDs?
• migraine – only anecdotal evidence– no controlled comparison of oral vs smoked
Relief of Spasticity (e.g., Multiple Sclerosis)
Relief of Spasticity (e.g., Multiple Sclerosis)
Glaucoma
Glaucoma (cont’d)
Potential Adverse Effects of Cannabinoid TherapyAdverse Effects Description