http://greendreamhealth.com/wp-content/uploads/2010/08/mm4.pdf
medicine.
Abstract
Advances in cannabis research have paralleled developments in opioid pharmacology whereby
a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic
significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The
major psychotropic CB delta-9-tetrahydrocannabinol (
Advances in cannabis research have paralleled developments in opioid pharmacology whereby
a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic
significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The
major psychotropic CB delta-9-tetrahydrocannabinol (
D9-THC) was isolated in 1964 and the
first CB receptor (CB1R) was cloned in 1990. CB signalling occurs via G-protein-coupled
receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic
acid that function in diverse physiological systems. Neuronal CB1Rs modulate synaptic transmission
and mediate psychoactivity. Immune-cell CB2 receptors (CB2R) may downregulate
neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models
demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception
and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have
suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia
have been limited by study size, heterogeneous patient populations, and subjective outcome
measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism.
They are currently licensed as antiemetics in chemotherapy and can be prescribed on a
named-patient basis for neuropathic pain. Future selective peripheral CB1R and CB2R agonists
will minimize central psychoactivity and may synergize opioid anti-nociception. This review
discusses the basic science and clinical aspects of CB pharmacology with a focus on pain
first CB receptor (CB1R) was cloned in 1990. CB signalling occurs via G-protein-coupled
receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic
acid that function in diverse physiological systems. Neuronal CB1Rs modulate synaptic transmission
and mediate psychoactivity. Immune-cell CB2 receptors (CB2R) may downregulate
neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models
demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception
and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have
suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia
have been limited by study size, heterogeneous patient populations, and subjective outcome
measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism.
They are currently licensed as antiemetics in chemotherapy and can be prescribed on a
named-patient basis for neuropathic pain. Future selective peripheral CB1R and CB2R agonists
will minimize central psychoactivity and may synergize opioid anti-nociception. This review
discusses the basic science and clinical aspects of CB pharmacology with a focus on pain
medicine.
