cannabinoids

Cannabinoids are a class of chemical compounds

that interact with the cannabinoid receptors in
the brain and body.
They are biologically active compounds used in
the management and treatment of
appetite/weight loss from HIV/AIDS and
chemotherapy in addition to epilepsy.
 Continues….
• They are very lipid soluble compounds thus
readily penetrate the brain cells to exert their
effects
• Cannabinoids have a range of effects including
psychoactive effects and non psychoactive
effects
• They are used for both recreational and
medicinal purposes
 Classes of cannabinoids
• Endogenous cannabinoids
 These are naturally produced in the human body.
Examples include anandamide (AEA) and 2-
arachidonoylglycerol (2-AG)
• Phytocannabinoids
 These are found in the cannabis plant (cannabis
sativa).
 The well known phytocannabinoids ae
tetrahydrocannabinol (THC) (found mainly in the
marijuana) and cannabidiol (CBD)
• Synthetic cannabinoids
 artificially manufactured cannabinoids which
are approved by Food and Drug Admnistration
(FDA) for medical purposes include
Dronabinol
Nabilone
 Cannabinoids receptors (CBR)
• Two receptors are found
• Cannabinoid receptor 1 (CBR1)
found mainly in the central nervous system and to some
extent in the peripheral
• Cannabinoid receptor 2 (CBR2)
found mainly in the immune system (have
immunomodulating effects)
• These receptors are said to be linked with G protein family
• Some are also linked to ion channels(like inwardly
rectifying potassium channels)
 Mechanism of action
• Action potential travels down the presynaptic
neuron thereby initiating neurotransmitter
release
• The action potential triggers the release of
neurotransmitters (like GABA or glutamate)
• Neurotransmitters released bind to the
postsynaptic neuron, transmitting the signal
across the synapse
 Mechanism continues……..
• In response to synaptic activity the postsynaptic
neuron synthesizes and release the
endocannabinoids (anandamide and 2-AG)
• Endocannabinoids travel retrogradely to the
presynaptic neuron and CB1 receptors
• Activation of the receptors inhibit the release of the
neurotransmitters from the presynaptic neuron
modulating synaptic transmission.
• The overall effect is therefore termed as negative
feedback
• Other exogenous cannabinoids (like
phytocannabinoid) interact directly with the
cannabinoid receptors thus mimicking the action of
endocannabinoids and leading to the same effects.
• AEA is hydrolyzed in postsynaptic neurons by fatty
acid amide hydrolase (FAAH) terminating its action
• 2-AG is hydrolyzed in presynaptic neurons, after
receptor activation, by monoacylglycerol lipase
(MAAG)
• The mechanism of action on CB2 receptor is
slightly different.
• Upon activation by endocannabinoid, this
receptor elicits many immnunomodulating
effects which depend on the cell type
• CB2 receptor can therefore modulate cytokine
release which has various clinical implications.
• Binding to the different parts of the central nervous system
mediates different psychotropic properties of cannabinoids,
particularly THC. These areas and end-effects include
• Hippocampus: impairment of short-term memory
• Neocortex: impairment of judgment and sensation
• Basal ganglia: altered reaction time and movement
• Hypothalamus: increased appetite
• Nucleus accumbens: euphoria
• Amygdala: panic and paranoia
• Cerebellum: ataxia
• Brainstem: anti-emesis
• Spinal cord: analgesia
 Clinical uses of cannabinoids
• They have various uses as follows
• Useful in treating certain forms of epilepsy (e.g., Lennox-
Gastaut syndrome and Dravet syndrome)
• Treating nausea and vomiting associated with cancer
chemotherapy
• Loss of appetite and weight loss associated with HIV/AIDS
• Useful in management of multiple sclerosis
• Tourette syndrome management
• Chronic pain management (especially for opioid dependence)
• Tetrahydrocannabinol (THC) was once used as anesthetic
agent due to its calming effects similar to opioids
 Adverse effects
• Adverse effects of cannabinoids exist on a spectrum,
ranging from mild to lethal.
• The most frequently encountered side effects of
cannabinoids are generally those from recreational
sources.
• Over the short-term, mild effects include
• euphoria, anxiolysis, tachycardia, visuotemporal
distortion, sensory amplification, tachycardia,
postural hypotension, conjunctivitis, hunger, and dry
throat, mouth, and eyes.
• More severe symptoms include
• panic attacks
• myoclonus, psychosis
• hyperemesis
• inhalation burns
• acute respiratory distress syndrome (ARDS)
• bronchospasm
 Toxicity
• long-term, heavy cannabinoid abuse has correlated in
numerous adverse health conditions, including:
• Addiction, altered brain development, and cognitive
impairment in adolescents
• Chronic bronchitis, ARDS, lung cancer
• Increased risk for myocardial infarction, stroke, and
thromboembolic events[
• Exacerbation of mood disorders (anxiety, depression) and
psychotic disorders (schizophrenia)
• Exacerbation of neurodegenerative diseases (multiple
sclerosis, Alzheimer disease, Parkinson disease)
 Toxicity management
• In the event of cannabinoid drug toxicity, as described
above, treatment and management are largely
supportive and focused on symptom relief.
• Psychosis and agitation are treated by benzodiazepines
and antipsychotics, (preferably of the second-generation
or atypical class, due to their lower risk of
extrapyramidal effects)
• An electrocardiogram can rule out myocardial ischemia
or dysrhythmias, and if present, the clinician should
start empiric therapy with rate-controlling agents.
• Hyperemesis should receive appropriate
medication with antiemetics provided that the
risk of dysrhythmias is sufficiently low.
• Clinicians need to address seizure activity with
benzodiazepines and/or anticonvulsant agents
as tolerated.
• Finally, signs of pulmonary compromise should
necessitate supportive measures such as
oxygen via nasal cannula, positive airway
pressure ventilation, and endotracheal