Drugs of Abuse: Drugs and Cannabis Flashcards
what system in the brain enables euphoria?
dopaminergic neurones from the VTA stimulate the release of dopamine into the NAcc in the reward system
what are the methods of drug administration?
o Intranasal (via mucous membranes in nasal sinuses) – slow absorption.
o Oral – very slow absorption.
o Inhalational – rapid absorption.
o Intravenous – rapid absorption.
what is the fastest route of administration to the brain?
inhalation- pulmonary circuit is very short
IV has to do the systemic circuit before reaching the brain
what are the main classification of drugs?
- narcotics (painkillers)
- depressants
- stimulants
- miscellaneous
examples of narcotics
opiate-like drugs e..g heroin
examples of depressants
alcohol
benzodiazepines (valium)
examples of stimulants
cocaine amphetamines caffeine methamphetamines nicotine
example of miscellaneous drugs
cannabis
ecstasy
these drugs have effects from multiple classes
what is the order of onset of euphoria in ascending order based on administration
oral< intranasal < IV, inhalation
what are the components of cannabis?
- cannabis sativa is the plant
- hashish/resin is the trichomes (glandular hairs that contain the highest concentration of THC)
- hash oil is the solvent extract
how many compounds in cannabis?
over 400, >60 of them being cannibinoids
what is the most potent cannabinoid?
delta 9-THC
what produces the positive effects of cannabis smoking?
the inclusion of cannabidiol may regulate the negative effects of delta 9 THC
how has dosage of THC changed over time?
Doses in 60’s and 70’s was ~10mg THC
Now it is 150-300mg of THC.
Potency has increased over the years; delta9-THC has increased, so has cannabidiol. Here, the negative effects are more pronounced
what are the route of administration of cannabis?
o Oral – 5-15% THC delivered.
o Inhalation – 25-25% THC delivered. Must be breathed in deeply
why is THC delivery lower when cannabis is taken orally?
delayed onset due to slow absorption with first pass metabolism
how does cannabis accumulate and leave?
- slowly accumulates in the body as it is very lipid soluble
- builds up fatty acid conjugates.
- Accumulation in poorly perfused fatty tissue with chronic use
takes 30 days for effects to cease
how is cannabis metabolised?
THC converted to a more potent molecule: 11-OH THC, a phase 1 metabolite
11-OH THC is more potent than delta 9 THC
how is cannabis excreted?
- GIT 65%:enters bile and is enterohepatically recycled due to its lipid solubility
- urine 25%
what is the difference in concentration of THC in the brain and the blood?
what is the effect of this?
THC is more concentrated in the brain (which is very fatty) compared to the blood due to the lipid soluble property of cannabis
therefore there is a poor correlation between plasma cannabinoid and degree of toxicity
what receptors do cannabinoids bind to ? where are they located?
- CB1 receptors in the brain: Hippocampus, cerebellum, cortex and basal ganglia
- CB2 receptors in the periphery: immune cells
what type of receptor is CBr?
inhibitory GPLR linked to adenylate cyclase
depresses cell activity
what is the endogenous version THC that normally binds to the CBr?
anandamide
result of fatty acid amide hydrolase inhibition
how does binding to CBr lead to euphoria?
binding of Cb1 receptors on GABA neurones inhibits the release of GABA. This has a disinhibition effect on the VTA neurone releasing dopamine. The inhibition on dopamine release is reduced so more dopamine is released
what effect does cannabis have on the anterior cingulate cortex (ACC)? what is the ACC?
ACC is involved in performance monitoring with behavioural adjustment.
Cannabis causes the hypoactivity of ACC
how does cannabis increase the need for food?
increase in orexin production:
- cannabis has effects on the lateral hypothalamus in two places:
- presynaptic inhibition of GABA increases MCH (Melanin Concentrating Hormone) neuronal activity.
- this increases food seeking behaviour
what are the major impacts of cannabis?
- euphoria
- CNS: psychosis, schizophrenia
- food intake/hunger/munchies
- memory loss
- tachycardia
- immunosuppressant
how does cannabis act on the immune system?
agonise CB2r on immune cells: o Macrophage. o Mast cell. o B-cell. o T-cell. o Natural Killer cell.
what are the central effects of cannabis?
o Psychosis, schizophrenia.
o Food intake – lateral hypothalamus.
o Memory loss – Limbic regions (Amnestic effects/decreased BDNF (Brain Derived Neurotrophic Factor)).
o Psychomotor performance – affects cerebral cortex.
what are the peripheral effects of cannabis?
o Immunosuppressant (CB2 binding on immune cells) o Tachycardia/vasodilation – via TRPV1 receptors (NOT CBr) leads to red eyes as conjunctiva vasodilate.
why is cannabis sometimes considered safer than alcohol?
cannabis does not effect the cardio-respiratory centre as much as alcohol (which surpasses the medulla) so its near impossible to overdose on cannabis and cause cardio-respiratory failure
why does cannabis not affect the cardio-respiratory centre much?
there is a low concentration of CB1r on the medulla
when can CBr be unregulated?
o MS/pain/stroke patients – to regulate pain.
o Fertility/obesity – this is pathologic and may contribute to obesity and infertility.
what are the autoprotective cannabis based drugs?
Dronabinol, Nabilone, Sativex
what is the use of dronabinol, nabilone?
anti-emetic in cancer
stimulate appetite in AIDS and chemo patients
what is the use of savitex?
used as analgesic for neuropathic pain in MS
what are the autoimpairment cannabis based drugs?
rimonabant
what is the use of rimonabant?
anti-obesity drug by blocking feeling of hunger (lateral hypothalamus)
decreases weight
off the market now due to depression side effect leading to suicide.
what is the active ingredient in cannabis?
delta 9 tetrahydrocannabinol
which receptors does cannabis bind to and where are these receptors?
CB1 receptors : found on GABA neurones (central)
CB2 receptors: found on immune cells (peripheral )
why does cannabis cause psychosis, schizophrenia?
- targeting the anterior cingulate cortex
- causes hypoactivity
- this increases agitation and fright
why does cannabis cause increased hunger?
- increases orexin activity
- orexinogenic activity stimulates the lateral hypothalamus
- lateral hypothalamus increases hunger
why does cannabis cause memory loss/amnesia?
- decrease in brain derived neurotrophic factor
- this is needed for memory formation in the hippocampus
why does cannabis cause tachycardia?
- binds to TRPV 1 (Ca2+) channels
- increases calcium influx
binding to TRPV also causes the red eyes
why does cannabis lead to a immunosuppressive effect?
- decreases B and T cell numbers
- NK cell activity decreases
binding to CB2
what is dronabinol?
what are its uses?
THC type used as anti-emetic in cancer patients and treating appetite loss in AIDS patients
what is sativex?
what are its uses?
THC/cannabidiol mixture
used to treat MS as it binds to CBr in the brain to depress activity (neuropathic pain is pain that originates from the CNS)
what is rimonabant?
what are its uses?
CB1 receptor antagonist
- blocks CB receptors in adipocytes (which cause obesity) there causes weight loss
however no longer in use due it increased depression and suicidal thoughts
