• alcohol
• barbituates and related compounds
• benzodiazepines
• gamma hydroxybutyrate (GHB)
• inhalants (volatile agents)
• cannabis (also has depressant effects)

• uncommon today, but use to be for relaxation, sociability
• low TI, so OD not uncommon, but it is dangerous
• withdrawal from these can be life threatening

• mainly seen in faster acting BZ's: alprazolam, diazepam
• physical dependence not uncommon w/all BZ's when used chronically

marijuana

hashish

oil

active ingredient, THC, will act at the cannaboid receptors (its usual endogenous ligand is anandamide)

• smoked
• eaten (slower and longer effects with oral use, but more likely to OD)

• synthetic THC available as schedule III: dronabinol
  • AIDS related anorexia
  • nausea with chemotherapy

• mechanism- cannabinoid R antagonist
• indications in europe: DM, obesity

Proposed to help treat drug abuse

• depressant like
  • relaxation, disinhibition, drowsiness, euphoria, slowed reflexes, impaired memory
• psychadelic like
  • intensified and/or distorted sensory input
  • altered sense of time and space
  • enhanced sense of meaning
  • empathy
  • paranoid
• sympathomimetic
  • increase HR
  • dry mouth
  • dry nose
• increased appetite
• reddening of conjunctiva
• decreased exercise tolerance
• dry mouth,

• little tolerance seen, instead behavioral "learning"
  • experienced users have greater subjective reponse (effect of "set")
  • setting also greatly influences subjective response
• little physical dependence, modest psychological dependence (variable)

• related to serotonin- LSD, psilocybin, DMT
• related to dopamine, NE- mescaline, MDA, MDMA (ectasy)
• deliriants- PCP, ketamine, antimuscarinics
• salvinorin A (active ingredient from salvia divinorum)

• sympathomimetic activity- flushing, dry mouth, tachycardia, sweating, tremor
• altered perception- heightened awareness, decreased discrimination of input, synesthesia; distorted sense of time, space, body image
• hallucinations (mainly visual)
• mood- highly labile (drom euphoria to panic and back) (can increase empathy)
• altered thought processes- sense of insight and enhanced meaning, disruption of logical thought, hypersuggestibility, depersonalization (loss of ego boundary), paranoia

Effects highly dependent on set (expectations) and settings

• little tolerance or dependenc seen
  • most not self administered by animals

• mechanism- anesthetic effect
  • inhibit NMDA glutamate receptor
  • ketamine is schedule III and PCP schedule II
• routes of administration- usually smoked, but also oral, IV, nasal

• sympathomimetic
  • increase HR
  • increase bp
  • sweating
• parasympathomimetic- salivation
• muscle rigidity, ataxia, increased strength
• blank stare, nystagmus
• loss of sensation

• analgesia/anesthesia
• delusions, illusions, confusion, hallucinations
• altered time, space, body perception
• disorganized thought, blocked speech
• amnesia
• emotional lability
• violent and/or bizarre behavior
• restlessness, repetitive purposeless movements
• at higher doses
  • seizures
  • coma
  • death

• pyschosis, exacerbation of preexisting psychopathology
• seizures, coma, death
• cardiac arrhythmia
• myoglobinuria, renal failure
• behavioral
  • accidents
  • violence
• afterwards
  • depression
  • delirium

• psychosis
• mood and PD's
• impaired memory, intellectual performance, speech disorders

• mechanism of action
  • active ingredient: salvinorin A
  • acts as agonist at kappa opioid receptor
  • reversible by opioid antagonist
• routes of administration: can be
  • chewed
  • smoked
  • taken as tincture
• very brief DOA (10 minutes)

• hallucination
• unpredicatble behaviors
• laughter
• unintelligible speech
• analgesia
• aftereffects- calming, dysphoric

• compounds
  • toulene
  • hexane
  • trichloroethane
  • trichloroethylene
  • chlorofluorocarbons
  • dimethyl ether
  • nitrous oxide
• sources
  • gasoline
  • glue
  • correction fluid
  • cans of whipped cream
  • solvents

• PK- very rapid onset with short DOA (min)
• effects
  • exhilaration
  • euphoria
  • drunkeness
  • hallucinations
  • perceptual distortion

• suffocation
• arrhythmias
• explosion
• injury
• chornic use cause brain damage

• injected
• oral

• increased confidence
• decrease fatigue
• heightened motivation
• agitation
• irritability
• insomnia

stimulatory effects

• nandrolone
• drostanolone
• oxandrolone
• testosterone
• androstenedione

• argumentative
• impetuous
• moody
• suspicious
• aggressive
• eventually, dangerous, violent, and antisocial behavior

• mechanism- stimulate secretion of GH
  • leads to increase muscle bulk and reduced fat
• effects
  • psychoactive effects
    • prolonged euphoria
    • sedative effects (via GABA)

• GHB
• clenbuterol (beta agonist)
• propanolol (beta blocker)
• EPO

• anabolic
• agitation
• bronchodilation

• increase cAMP
• increase CREB
• increase FOSB

leads to tolerance, sensitization, dependence

• increase CRF
• increase glutamatergic
• decrease dopaminergic and serotonin
• increase noradrenergic

• acute tx of OD
• detox
• amelioration of withdrawal symptoms
• maintenance with less dangerous alternative
• "cure"

• tolerance is reversible
• drug addiction persist for years and craving continues long after drug adminstration has ceased
  • leads us to believe likely development of addiction due to rewiring of synaptic remodeling of brain similar to that involved with learning and memory

• male
• h/o dependence in close relative
• preexisting psychiatric diorders may predispose to substance use
  • conduct disorder, antisocial PD, ADD
  • bipolar and anxiety disorders

• use chronic disease model (ex: DM, asthma) rather than acute disease (ex: pneumonia)
  • likelihood of achieving long term abstinence improved by treatment
  • counseling is very important component in all forms of tx
  • due to substance use disorders being chronic and relapsing in nature, positive outcomes related to duration and intensity of tx

uncomfortable but not life threatening and the opposite of acute effects

• hyperalgesia
• muslce aches
• diarrhea
• nausea
• cramps
• sweating
• fever
• dilated puplis
• HTN
  yawning
• piloerection
• restlessness
• irritability
• dysphoria
• anxiety
• craving for opioids

• methadone- remember there is cross dependence, so we can sub with something with more favorable properties

• methadone reduces heroin craving
• addicts are not commiting crimes to obstain drug
• dangerous IV drug use is avoided
• users must interact with health care providers and counseling is provided
• kinetics of oral methaodone vs. IV heroin are more conducive to leaiding productive lives

• heroin (half life: 3-4 hrs) cause swings between high/largely dysfunctional and feeling sick/withdrawal
• methadone (half life: 6-8 hrs) helps to avoid sharp peaks and valleys so they can lead productive lives while on the drug

• its much easire because the withdrawal symptoms are related to acute kinetics
• withdrawl less intense, longer in duration, but more tolerable

• detox and meaintanance
• adverse effects- some initial depression (if persist, treat with antidepressants)

• methadone
• LAAM
• buprenorphine
• naltrexone
• clonidine

• very long acting oipoid
• take 2-3 times a week

• partial agonist at mu receptor, so difficult to OD
• will block effects of other agonists, so withdrawal is milder than from heroin

• helps amiliorate opiod withdrawl symptoms

• nicotine replacement therapy: gums, patches, nasal spray
• limited success- different kinetics, and doesnt address behaviorl aspects

• varenicline
• bupropion
• nicotine replacement therapy

• mechanism of action- partial agonist at alpha 4 beta 2 CNS nicotinic R
• adverse effects
  • sleep dream disturbances
  • anxiety
  • depression
  • suicidal ideation

• classified as antidepressant, but can be used with nicotine replacement therapy to improve results