Week 8 - Cannabis Flashcards
Cannabis plant
- Cannabis sativa
- plants vary in size; male and female plants
- female plant must fertilized by pollen from male plant to generate seeds
- female plant produces sticky resin at top to attract pollen and protect seeds
Active ingredient in cannabis
- over 60 cannabinoids (all found only in cannabis)
- amount of delta-9-THC depends on preparation, route of admin and inactive ingredients altering potency or metabolism
- all parts of plant contain THC
- burning cannabis, GI digestion & metabolism can create new cannabinoids
Forms of cannabis
marijuana: dried leaves & flowers; usually smoked (joint or bong)
hashish: dried resin from female plant; usually smoked, eaten (foods)
hash oil: hashish boiled in alcohol, then residue is filteres & alcohol evaporated; can be smoked
concentrates: extracts (dabs, wax, shatter) use butane hash oil as solvent & vaporised in small quantities (high THC)
edibles: foods containing cannabis
medicinal cannabis - TGA approved, capsules/oral solutions
THC content of plants
changes over time
60s - 1.5%
90s - 3.5 - 4.5%
2008 - 10%
can be as high as 30% but typically contain 3-15% THC
industrial hemp contains < 0.5-1%
uses of cannabis
- fibre (clothes, textiles, paper, rope)
- oil (lamp oil & food) and as an active ingredient in the manufacturing of soap, paint & varnish
- medicinal purposes
- psychoactive properties
Pharmaceutical canabinoids
- Marinol & nabilone: to alleviate nausea and vomiting in people w/ cancer; anorexia & weightloss assoc AIDS
- sativex: neuropathic pain assoc multiple sclerosis
- epidyolex: seizures assoc rare epileptic disorders
historical medical uses
- rheumatism
- mania
- whooping cough
- asthma
- bronchitis
- spasms
- epilepsy
- convulsions
- palsy
- uterine haemorrhage
- dysmenorrhea
- hysteria
- alcohol withdrawal
- loss of appetite
Oral administration
slow absorption by this route, but long duration of effect - affected by first pass metbolism by liver
- not ionized pKa = 10.6
- extremely lipid soluble
- onset of action: 30-90mins >ingestion
- peak: 1-4hrs after ingestions; psychoactive effects may last 4-12hrs, appetite >24hrs
inhalation
readily and rapidly absorbed
- 10-25% of cannabinoids reach general blood circulation from lungs
- peak blood levels <10 mins; peak effects: lags about 30 mins
- holding smoke does not increase absorption
- depth and frequency of inhalation may alter THC absorption
- vaporizers now popular method
distribution
- distributed to all areas of body (capable of altering all biological systems)
- concentrated in lungs, kidneys, liver
- ~1% enters the brain but levels continue to increase after ingestion & peak blood levels
- crosses placenta and is present in breat milk
excretion
- initial metabolism in lungs or gastrointestinal tract depending on admin
- most metabolism in liver; CYP450 enxymes
- delta-9-thc and 11-hydroxy-delta-9-THC are more lipid soluble and harder to excrete than other metabolites (> 100)
- 11-hyroxy-delta-9-THC is more active than delta-9-THC and penetrates BBB easier
metabolism of other cannbinoids
cannabidiol (CBD) - 20 metabolites
- blocks enzyme that metabolizes THC
cannabinol (CBN) - 20 metabolites
- increases metabolism of THC
- possible interaction effects between THC, CBN & CBD to displce THC from blood binding sites (increases amount available for distribution
excretion: THC
Phase 1:
- 1/2 life ~ 30-80 minutes; redistribution effect
Phase 2:
- 1/2 life ~ 20-30 hours; metabolism effect
- slow metabolism due to lipid solubility & speed that THC is released from fatty tissues - traces of THC can be detected 1-4 weeks after ingestion
- excreted in feces (65%) and urine (20&
- effects of frequent use on metabolism unclear
CBD half life 9-32 hrs
Receptor sites
- 2 known types of cannabinoid receptors (CB1 & CB2)
- work on second messengers & neuromodulators
CB1
- Located in CNS
- uneven distribution of receptors in the CNS
- most in higher centres therefore affect memory, emotional expression, mental processes; but also affect movement, appetite & analgesia
CB2
- mostly outside the CNS in spleen & immune system; could account for effects on immune functioning
- in CNS ; glial cells, stem-like cells and other brain areas
Endogenous Ligands (endocannabinoids)
- anandamide
- fat soluble, but simpler molecular structure
- exact function unkown
- discovery has lead to abundance of research
function of endocannabinoids: relax, eat, sleep, forget & protect
THC & endocannabinoids alter the functioning of
GABA, NE, DA, seratonin (5-HT), ACh, histamines, glutamate & opiod peptides
how are endocannabinoids synthesized?
on-demand in dendrites & cell body then released, cross synapse & bind to presynaptic CB1 receptors - due to binding they have a retrograde action
what is retrograde action?
allows the postsynaptic neuron to shut down presynaptic neuron which causes a depolarization induced suppression of inhibition and excitation (DSI & DSE)
3 types of neuromodulation
Increased synthesis of:
- NE
- DA
- 5-HT
- GABA
alter receptors for:
- NE
- ACh
- DA
- potentiate action of:
- NE
- ACh
- DA
Reinforcing effects of cannabinoids
- CB1 receptors located with dopamine receptors in mesolimbic dopamine pathway regions (midbrain, pfc, basal ganglia)
- CB1 receptor stimulation decreases inhibitory actions of GABA neurons projecting on to dopamine neurons in the nacc
- positive dopamine neurons in the ventral tegmental area synthesise & release endocannabinoid when stimulated
Reinforcement via opioid receptors
- CB1 overlap & interact with mew opiod receptors in nacc
- mew opioid receptor abolishes preference to THC
- naloxone (opioid antagonist) blocks THC self-administration & THC induced dopamine release in nacc
- naltrexone decreases cannabis use and positive subjective effects in daily marijuana smokers
- CB1 reinforce effects and devt of phys dependence of some opioids (morphine & heroin)
Low-moderate dose effects on body
- dilation of small blood vessels in eyes
- dry mouth, thirst
- hunger (max 3hrs after smoking; tolerance after few weeks)
- decreased blood pressure @ low doses/repeated use - increases @ high dose
- body temp changes
- increased heart rate
- increased cortisol
- headache, dizziness, nausea/vomiting
