alcohol and cannabinoids

lecture given 3/16/2026

alcohol is the most…

widely used drug in the world

14 million US adults have alcohol use disorder, 178,000 deaths from alcohol related causes per year

what is a standard drink?

any drink that contains 14g or 18ml of pure alcohol

12 oz of beer, 5 oz of wine, 1.5 oz of distilled spirits

low risk drinking in men and women

men: < or = 2 standard drinks per day

women: < or = 1 standard drink per day

heavy drinking in men and women

men: > or = 15 standard drinks per week

women: > or = 8 standard drink per week

binge drinking in men and women

men: > or = 5 standard drinks per ~2 hrs

women: > or = 4 standard drink per ~2 hrs

alcohol use disorder (AUD)

compulsive alcohol use, loss of control over intake, continued use despite harm

why is AUD relevant to dentists?

heavy alcohol use increases risk of sedation complications, bleeding disorders, and impaired healing

low blood alcohol levels (BAC 0.02-0.05%)

mild euphoria, reduced anxiety, impaired judgement and inhibition

moderate blood alcohol levels (BAC 0.05-0.10%)

impaired coordination and reaction time, slurred speech, reduced attention and decision-making

high blood alcohol levels (BAC > 0.10-0.20%)

marked motor impairment, confusion, ataxia, memory impairment (blackouts)

very high blood alcohol levels (BAC > 0.30%)

respiratory depression, coma, potentially fatal alcohol poisoning

what are the absoprtion pharmacokinetics of ethanol?

absorbed in mouth and stomach, but mostly from intestine

rapid absorption- blood levels peak 30-60 minutes after ingestion

decreased by presence of food (fat) in stomach by half

what are the distribution pharmacokinetics of ethanol?

highly water soluble and distributes into total body water (blood, extracellular fluid, intracellular fluid)

because it does not partition into fat, distribution depends on body water volume

organs with high blood flow (brain, liver) reach equilibrium rapidly

clinical implication-- females have a lower total body water (higher body fat %) so they will have a higher BAC for the same amount of alcohol

what are the metabolism pharmacokinetics of ethanol?

90-95% metabolized in the liver

primary pathway- alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde / aldehyde dehydrogenase (ALDH) converts acetaldehyde into acetate / acetate is further metabolized into CO2 and water

secondary pathway (important in heavy drinkers)- microsomal ethanol oxidizing system (MEOS), enzyme involved CYP2E1

what product of alcohol metabolism is toxic, and what does it cause?

acetaldehyde

causes flushing, nausea, and headache

what are the elimination pharmacokinetics of ethanol?

major pathway- (dominant metabolic pathway in liver) ADH becomes saturated quickly (zero order kinetics), a constant amount is eliminated per hour, average rate of 7-10g per hour

secondary pathway- MEOS- follows 1st order kinetics, contribution increases at higher ethanol concentrations, induced in chronic alcohol use (increases metabolism of some drugs, incresases formation of toxic metabolites)

minor elimination- 2-10% is excreted unchanged in breath, urine, sweat (basis of breathlyzer testing)

alcohol enhances sedative effects of which drugs that depress the CNS?

benzos, opioids, barbiturates, first generation antihistamines

causes excess sedatin, impaired coordination, respiratory depression

what are the metabolic interactions with acute alcohol use?

inhibits drug metabolism, increases blood levels of some drugs

what are the metabolic interactions with chronic alcohol use?

induces CYP2E1 and other CYP enzymes

increases metabolism of some drugs, increases formation of toxic metabolites

what drug interacts with alcohol to increase the risk of bleeding?

NSAIDs- increased gastric mucosal damage, increased GI bleeding risk

anticoagulants- aucte use increases anticoagulant effect, chronic use decreases anticoagulant effect

what drug interacts with alcohol to increase the risk of hypoglycemia?

antidiabetic drugs- inhibits hepatic gluconeogenesis, increases risk of hypoglycemia

why is it bad to mix alcohol and acetaminophen?

acetaminophen is mainly metabolized by glucuronidation and sulfation, but a small fraction is metabolized by CYP2E1 (toxic metabolite NAPQI), NAPQI is detoxified by glutathione (GSH)

acute alcohol use competes for CYP2E1, may temporarily decrease NAPQI formation HOWEVER chronic alcohol use induces CYP2E1 which increases NAPQI formation and the risk of liver injury, decreases hepatic glutathione (GSH) which reduces the detoxification of NAPQI

t/f ethanol is a CNS stimulant

false!- sedative hypnotic that depresses the CNS in a dose-dependent fashion

the apparent stimulation results from disinhibition of CNS function because of the selective depression of inibitory pathways at lower concentrations of ethanol

higher doses (intoxication) lead to overall depression of the CNS

what effect does alcohol have on endogenous opioids?

induces the release of them

induces release of endorphins into the VTA and NAcc (unclear whether it is the arc pathway)

it inhibits an inhibitor

what effect does alcohol have on GABA a receptors?

enhances GABA mediated Cl- influx, results in neuronal inhibition

leads to sedation, anxiolysis, impaired coordination

what effect does alcohol have on NMDA glutamate receptors?

it decreases Ca2+ influx through NMDA channels

results in reduced excitatory neurotransmission

t/f GABA a receptors are inhibitory and NMDA glutamate receptors are excitatory

true- that’s why ethanol net effect is CNS depression (increased inhibition and decreased excitation)

t/f in a normal state, there is a balance between glutamate/NMDA (excitatory) and GABA a (inhibitory) signaling but this is disrupted with ethanol

true

what is the mechanism of ethanol withdrawl?

chronic alcohol exposure causes neuroadaptations- decreased GABAergic inhibitory signaling, increased NMDA glutamate receptor activity

when alcohol is suddenly stopped- loss of inhibition and excess excitation, CNS hyperexcitability

what are early clinical manifestations of ethanol withdrawl?

6-12 hrs

tremor, anxiety, irritability, nausea, sweating, tachycardia, hypertension

what are intermediate clinical manifestations of ethanol withdrawl?

6-48 hrs

withdrawl seizures

what are severe clinical manifestations of ethanol withdrawl?

48-96 hrs

delirium tremens (DTs), agitation, confusion/delerium, hallucinations, autonomic instability

what is the treatment for ethanol withdrawl?

benzos!

enhance GABA a receptor activity, restore inhibitor tone in the CNS

ethanol withdrawl reflects…

rebound CNS excitation after chronic CNS depression

what are the major complications of chronic alcohol use?

liver disease- fatty liver to hepatitis to cirrhosis

pacreatitis

CV disease- alcoholic cardiomyopathy, hypertension

peripheral neuropathy

malnutrition and vitamin deficiencies

wernicke-korsakoff syndrome

caused primarily by thiamine (vitamin B1) deficiency in chronic alcohol use

wernicke encephalopathy (acute)- confusion, ophthalmoplpegia / vision changes, ataxia

korsakoff syndrome (chronic)- severe memory impairment, confabulation

alcohol use disorder often leads to malnutrition and impaired ____ absorption, resulting in _______ and brain ______

thiamine, neurodegeneration, atrophy

disulfiram (antabuse)

blocks acetaldehyde dehydrogenase causing excess build up of acetaldehyde

due to build up of acetadehyde, patients may feel nausea, vomiting, have headaches or chest pain after only 5-10 min of drinking

naltrexone

mu opioid receptor antagonist

blocks endogenous opioid mediated reward from alcohol- reduces euphoria and craving

helps reduce relapse

adverse effects of nausea and hepatotoxicity at high doses

acamprosate

modulates glutamate and GABA neurotransmission

reduces NMDA mediated excitatory signaling

helps restore excitatory-inhibitory balance altered by chronic alcohol use

clinically reduces craving and relapse

adverse effects of diarrhea

which drugs are used in acute ethanol withdrawl?

benzos and thiamine

which drugs are used in chronic alcoholism?

naltrexone, acamprosate, disfulfiram

what are the orofacial findings of chronic ethanol use?

sialosis- parotid gland enlargement (painless bilateral parotid enlargement), associated with autonomic dysfunction and metabolic changes

increased bleeding tendency- liver disease leads to decreased clotting factor synthesis, this can complicate dental procedures

higher risk of oral premalignant lesions- leukoplakia, erythroplakia, increased risk of oral squamous cell carcinoma and risk is greatly increased with alcohol AND tobacco

patients with AUD often have…

poor oral hygiene, increased tooth loss, severe periodontitis, delayed wound healing

what drug considerations need to be made when prescribing for an AUD pt?

avoid high doses of acetaminophen

alcohol + NSAIDs leads to increased bleeding risk

methanol

present in denatured alcohol, industrial reagent, solvent in paint removers

absorbed orally, by inhalation, and through skin

what are the effects of methanol?

blurry vision and even blindness, acidosis due to formic acid production

CNS depression (<ethanol) and sudden respiratory depression

what is the treatment for methanol?

if methanol in blood is > 50mg/dL, do hemodialysis

ethanol (competes for ADH) or fomepizole (ADH inhibitor)

sodium bicarbonate (for acidosis)

ethylene glycol

present in antifreeze (sweet taste) and in heating systems

metabolized to toxic aldehydes and oxalate- CNS depression, hyporeflexia and tetany / CV signs and congestive heart failure, renal damage

treatments are the same as methanol

what are the major compounds that cannabis sativa contains?

delta 9 tetrahydrocannabinol (THC)- primary psychoactive compound

cannabinol (CBN)- 1/10 THC

cannabidiol (CBD)- non-intoxicating

what system do cannabinoids act through, and how?

endocannabinoid system

endogenous ligands- anadamide (AEA) and 2-arachidonoyglycerol (2-AG)

cannabinoid receptors- CB1 receptors (abundant in CNS, mediate psychoactive effects), CB2 receptors (mainly immune cells, modulate inflammation)

what is the mechanism of action of cannabinoids?

endocannbinoids are synthesized on demand from membrane lipids in the postsynaptic neuron

they diffuse retrogradely across the synapse to the presynaptic terminal

bind to CB1 receptors (Gi-coupled GPCRs) on presynaptic neurons

CB1 activation- decreases Ca2+ influx which decreases neurotransmitter release

neurotransmitters affected include glutamate, GABA, and others

what is the result of cannabinoids?

altered cognition and memory, sedation and impaired coordination, modulation of pain signaling, activation of reward pathways

what are the acute effects of cannabis?

CNS (CB1 mediated)- euphoria, relaxation, altered perception of time, impaired memory and attention, impaired coordination and reaction time (driving risk)

physiologic effects- tachycardia, conjunctival injection (red eyes), vasodilation / flushing, increased appetite

at higher doses- anxiety or panic, paranoia, psychosis in susceptible individuals

what are the oral findings of cannabis use?

xerostomia, increased periodontal disease, leukoplakia like lesions may occur

cannabis smoke contains carcinogens- possible oral cancer risk

possible increased oral infections due to immunosuppressive effects

what do dentists need to keep in mind with cannabis using pts?

additive CNS depression with sedatives or opioids

cannabis may cause tachycardia and anxiety- cautions with epi containing anesthetics

cannabinoids may inhibit CYP enzymes- potential drug interactions

avoid elective procedures if pt is acutely intoxicated

what is the mechanism of action of cannabinoids in the reward pathway?

activate CB1 rececptors in the VTA

CB1 activation inhibits GABA release from interneurons

reduced GABA inhibition disinhibits DA neurons

results in increased DA release in the nucleus accumbens

outcome is activation of the mesolimbic reward pathway and contributes to reinforcement and abuse potential

marijuana withdrawl syndrome

clinically seen in pts who use daily and suddenly stop

symptoms are craving, decreased appetite, weight loss, restlessness, sleep difficulty, aggression, irritability, insomnia, anxiety, depressed mood, psychosis

what are the therapeutic uses of cannabinoids?

antiemetic effects- chemotherapy induced nausea

appetite stimulation- AIDS related wasting

analgesic effects- neuropathic pain

MS spasticity

glaucoma- decreases intraocular pressure

dronabinol (marinol)

synthetic THC, used for chemotherapy induced nausea, appetite stimulant

nabilone (cesamet)

synthetic cannabinoid similar to THC, used for chemotherapy induced nausea

cannabidiol (epidiolex)

purified CBD, used for severe epilepsy

what are common adverse effects of prescription cannabinoids?

sedation, dizziness, impaired cognition

the symptoms resulting from the combination of disulfiram and alcohol are:

a) hypertensive crisis leading to cerebral ischemia and edema

b) nausea, vomiting

c) respiratory depression and seizures

d) acute psychotic reactions

b) nausea, vomiting

indicate the drug which decreases the craving for alcohol or blunts pleasurable high that comes with renewed drinking:

a) disulfiram

b) amphetamine

c) naltrexone

d) diazepam

c) naltrexone

which of the following is a major psychoactive component of cannabis sativa?

a) cannabidiol (CBD)

b) cannbinol (CBN)

c) tetrahydrocannabinol (THC)

d) anandamide

c) tetrahydrocannabinol (THC)

which of the following is an endogenous cannabinoid (endocannabinoid) that binds to CB receptors?

a) dronabinol

b) anandamide

c) nabilone

d) nabiximols

b) anandamide