final pmcol study - cannabis (17 + 18)

cannabis - sources

emergent view → only ONE lineage of cannabis species → prod. actual phytocannabinoid chemotypes (THC + CBD)

• therefore no real difference b/w sativa/indica — thought to be same ONE lineage of sativa

• cannabis species lineage = heads → prod. phytocannabinoid chemotypes (THC + CBD) + terpenes (function probably something to benefit plant lol)

*experience = entirely dependent on what chemical (THC + CBD) you consume

cannabis extraction + legalization effects

*cannabis extraction → resin ஃ can be used to make 2’ gen cannabis products

• done via solvent or solvent-less extraction ஃ super-critical extraction

*goal → make a super high purity or a single isolated compound

legalization → new forms of cannabis

• pre rolls + flower → extracts → topical

• extracts → vapes + beverages + edible

how to calculate THC

% = mg per g — ஃ mg/1000mg

• ஃ 15% = 150 mg TOTAL THC /1g ஃ 150 mg / 1000 → 15%

basically recall that 1g can be replaced by 1000 mg

• 17.3% → 173 mg / 1000 mg → 170 mg present

*basically recall that to make it a percentage — u gotta divide by 100 ஃ to cancel out the 3rd 0 in 1000, the numerator gotta have a zero also ஃ the percentage → into mg = has to be in 100ths place

• 0.5 g, TOTAL THC = 107mg = whats the percentage

• 107/0.5g → 214 mg/1g ஃ 214 mg/1000mg → 21.4%

BASICALLY USE TOTAL THC IN CALCULATION !!!!

THC vs total THC (THC + THCA) per unit — explain fluff

• total THC = includes inactive actid form ஃ its whats we are metabolizing TO TURN ACTIVE which is more cognizant of the TOTAL effects of THC

• main psychoactive effects = come from the conversion of THCA to active THC (THC content in the actual blunt doesnt account for the FULL psychoactive effects — the THCA content does!)

cannabinoids can be __

can be psychoactive, non psychoactive, synthetic

• in plant → THC + CBD exist mainly in acid/inactive form ஃ exist in THCA form

THC acid/CBD acid

in plant form:

THC acid → metabolized to psychoactive THC → elicites psychoactive effect

CBD acid →

• antioxidant,

• anti convulsant,

• anti-inflammatory,

• anti anxiety,

• anti psychotic,

• neuroprotective

cannabinoid ADME + how to have effective administration + absorption/metabolization

ABSORPTION + ADMINISTRATION:

inhalation (smoke), injestion, oral/sublingual (injest) + topical

• smoked → done via joints, pipies, bongs + vaporizers — administration → maximize absorption

*water bongs can ↓ harmful components + ↓ lung irritation

• THCA (non psychoactive precursor) + heat/pressure → converts into psychoactive THC

• ingested → slower onset effect, ↓ predictability of action BUT user’s control ↑

*looks like that eating/injesting cannabis = produces MORE PRONOUNCED EFFECT from the creation of metabolites in liver

• metabolites → offer strengthened effects

absorption:

→ THC is VERY LIPID SOLUBLE ஃ passes into BBB (brain)

metabolization → CYP450

• metabolites = stay in body (days/weeks)

comparing cannabis + cigaratte smoke

both involve combustion → creates smoke = liquid/solid particulates + gases

cigarette smoke + cannabis = similar levels of:

• tar, CO, acetylaldehyde, acetone, benzene, toluene, benzopyrene, HCN

cannabis smoked = has poorer filtration ஃ more airway irritation →

• dont have the filters like cigarretes would

• toking (deep inhalation to maximize THC absorption) → leads to choking (deep inhalation of these compounds ; tar, acetylaldehyde, acetone, CO, etc) triggers cough reflex

*cough reflex = constantly happens ஃ ↑ chronic coughing + risk of bronchitus

*cannabis doesnt have distinct link to lung cancer risk or COPD

• utilizing water bongs, dabs = ↓ harmful components + ↓ irritation

endocannabinoid receptor biology:

endogenous CBR ligands

→ arachidonoyl ethanolamide (AEA) (1992)

→ 2-arachidonoylglycerol (2-AG) (1995)

CB1 (considered psychoactive) → expressed in CNS (basal ganglia, cerebellum, hippocampus, cortex, amygdala)

• also found in eyes, pancreas, liver, skin, uterus and testes

• also hypothalamus + cortex

CB2 (considered immunity)→ immune cells, spleen, tonsils, + hippocampal neurons

physiological mechanism:

THC → pleasure, reward, + enhanced perceptions (everything is funny lol + time looks longer)

*CB1 activate = block pain transmission → analgesia

considered stimulant (dose dependent)

• heart rate ↑, skin vessel vasodilation, salivary gland vessel constrict in mouth ஃ (dry mouth)

• eyes = bloodshot (from ↑ vasodilation)

CB1 → hypothalamus, pancreass + liver = ↑ energy metabolism, ↑ appetite + thirst

• in hypothalamus → influence sex drive, sperm product., fertilization, implantation, fetal development + sucking in newborns

• hypothalamus → DA + 5HT release

cellular mechanism of action - what type of signalling + bind to what receptor

retrograde signaling — cannabinols modulate release of other NT

• CB1/2 =gi linked (inhibitory)

• TRPV1/2 receptors = Na+ + Ca2+ influx channels (involved in pleiotropic signaling ஃ multiple downstream targets + effects)

• 5HT2 sub type receptors

mainly gaba inhibition lolz

tolerance + withdrawl

regular use of cannabis = tolerance

• ↑ metabolism of CYP450 + ↓ CB1 receptor (↑ in CB1 internalization obvi)

• ↓ high, hypothermic (feel cold), ↓ cardiovascular, ↓ analgesia + locomotor + immune effects

withdrawl

• mild burn out (lethargy + apathy)

• chronic users = retain higher concentration of converted THC metabolites ஃ ease withdrawal effects elimination over months

*withdrawal symptoms aren’t as severe or insufferable lol

dependence

limited but a little psychological

• less dependence compared to other drugs of abuse BUT yes there’s addiction of course

ஃ since it’s really psychological based ஃ abstinence/ fix cannabis dependence is led through psychological therapy/approaches

acute adverse effects (so like immediate sucky)

1. Green out → basically induced vomit, nausea, complicated 5HT signalling

2. HIGH THC = impact learning ஃ memory ↓ + concentration/attention/reaction time ↓ (due to hippocampus effects)

• LTP IS LIMITED BY USE OF THC

3. recall 5HT complications → psychosis/paranoia, hallucination, delusions of control + grandiosity + anxiety = present

4. Heart rhythm complications (sympathomimetic)

5. lowkey the cannabis itself can be contaminated with pesticide → u bouta be gone like a bug bruh

6. hand eye coordination also fuh so it may impact driving !!

*stoned drivers may be defensive drivers = autonomic functions REALLY impacted BUT stoned drivers are extremely aware of impairment ஃ do behaviors to be more safe

• however things like fast rxn time + unconscious things = impaired so bad

• basically DONT DO IT → doubles risk of severe/injury + death

• synergistic effect when combined with alcohol, even like hella low doses (subeffective doses)... if used together→ impairment

7. if the cannabis is black market → risk of contamination

• rat poison (bodifacoum) → lead to severe bleeding

long term health risk

1. ↑ chronic cough ஃ bronchitis

2. ↓ repro (↓ egg implantation + ↑ miscarriage rates) + ↓ ovulation → result in low birth weight of baby

3. ↓ Testosterone, ↓ Sperm count + chance of abnormal sperm product (like side swimming sperm)

though most effects = considered reversible

4. Can be a GATEWAY DRUG - ‘

cancer could be of discussion but like… differing tests i guess

• though smoking cannabis could be good since it does have antioxidants

how can personal selection of cannabis help people in their own personal issues

tailor the therapeutic effects to the individual + disease they’re dealing with ஃ personalized cultivar selection

• like u could ask for medical advice to solve a type of issue like sleeping .. kinda like that basis but in a professional sense

difference between vaporize (vape) vs smoking

volcanos + vape → ↑ long term cough + bronchitus

• volcanos = THC administration w/o the CO concern/delivery)

• combustion + pyrolsysis (HIGH HEAT + O2) of plant → carcinogens (volcanos dont do this)

CO (carcinogens) = a byproduct of combustion/pyrolysis (which is O2 + HIGH TEMP) of PLANT TISSUE — volcanos dont go to this high of a temp ஃ no carcinogens produced

• Vaping → prod. decarbed THCA w/o burning ஃ does not produce carcinogens

• THC + THCA vaporizes @ 157 C ஃ boiling at 157 = only feel those effects of THC without burning too high → carcinogen

ஃ can CONTROL TEMPERATURE of whats components get boiled off in the smoke (HIGH, MID, LOW etc) ஃ cultivate personalized experience

entourage effect

effect where the all chemicals inside cannabis = work together → ↑ assist/elevate the effects of the OTHER compounds + their interactions with CB1 receptors

• form of synergism basically → chemical interactions with receptors enhance each OTHER’s effects

mechanism of reinforcement:

clinical exp:

• ↑ (5mg/kg iv dose) rats DA by 100%

• ↑ (8mg inhaled) humans DA by 136%

*saw that those ate orally = ≠ a significant increase (no measureable DA increase)

the increase in DA is mediated by the CB1 presynaptic retrograde inhibition mechanism 🙂

• dishinibition of DAergic VTA → activate NAC (ஃ ↑ addiction)

striatial release of of THC → under schizophrenia

cannbinoid detection test:

coloricmetric-elisa/dipsticks (most used

immunoassay/lateral assay

• roadside screenings = typically lateral flow assays

gas chromotography mass spectometry (GCMS)