Opiates SedativeHypnotics Cocaine Amphetamines Stimulants PCP Hallucinogens Symptoms

Opiates, Sedative/Hypnotics, Cocaine, Amphetamines, Stimulants, PCP, Hallucinogens Symptoms of intoxication and withdrawal Sergio Hernandez, MD – Dept. of Psychiatry

Road Map • Terminology • Cocaine • Amphetamines • PCP • Hallucinogens • Cannabis • Sedative/Hypnotics & Alcohol • Opiates

By the end of this lecture… • State the mechanism of action of ALL the drugs • • • discussed. Recognize the signs and symptoms of intoxication, particularly opioids, cocaine, PCP, hallucinogens. Recognize the signs and symptoms of withdrawal, particularly opioids, benzodiazepines, and alcohol. State how to treat opioid, benzodiazepine, and alcohol withdrawal. State which withdrawals can kill. State why smoking substances is so addictive.

Terminology • Intoxication: maladaptive behavior associated with drug ingestion. • Tolerance: need for more of a substance to become intoxicated (or same amount producing a decreased effect). • Withdrawal: development of syndrome following cessation of (heavy) use.

Terminology • Abuse: a maladaptive pattern of substance use resulting in repeated problems and adverse consequences. • Dependence: psychological or physical need to continue taking the substance. • • Psychological: (habituation) craving Physiological: (tolerance) a need to continue taking the substance to prevent withdrawal.

Terminology • New DSM 5 terminology: • Substance use disorder • • Particular substance should be specified Severity should be specified

Substance Use Disorder • Problematic pattern of use of a substance • Significant impairment or distress demonstrated by 2 or more of the following. • Within a 12 month period

Use Disorder Criteria • Taken in larger amounts or longer period than intended. • Persistent desire or unsuccessful efforts to cut down or control use. • A lot of time spent trying to obtain, use, or recover from use. • Craving, strong desire or urge to use.

Use Disorder Criteria Continued • Recurrent use causing failure at major obligations (work, home, school). • Continued use despite recurrent social or interpersonal problems cause or worsened by use. • Important activites given up or reduced because of use (work, social, recreation).

Use Disorder Criteria Continued • Recurrent use in physically hazardous situations. • Use is continued despite knowledge of problem. • Tolerance (need more or decreased effect with same). • Withdrawal.

Cocaine • Coke • Snow • Blow • Crack • Rock • Nose candy • White horse

Cocaine • Coca leaves have been used in South America for thousands of years. • Native tribes would dry the coca leaves, grind them into a fine powder, and mix them with woodash or crushed sea shells. • The sea shells would enhance absorption by decreasing the p. H of the mixture.

Cocaine In 1859, cocaine was isolated from the leaf of the Erythroxylon coca plant. Cocaine was added to many medications and tonics soon thereafter. Vin Mariani is a popular example that contained 8 mg per glass (a popular drink among Tour de France riders).

Cocaine • Many well respected members of society used • • cocaine openly, among them Freud and Halsted (and Sherlock Holmes). Sigmund Freud became a famous proponent of cocaine when his friend, scientist, Ernst von Fleischl became addicted to morphine following surgery. Initially von Fleischl did well, but a few years later was injecting up to a gram per day.

Cocaine • Coca-Cola contained • a few milligrams of cocaine when first introduced in 1886. In 1903, Coca-Cola replaced its cocaine with caffeine when its potential for addiction became known.

Cocaine • • • May be snorted, injected, or smoked. Injection and smoking provide the highest and most rapid increase in blood levels. Freebasing: refers to stripping cocaine of its hydrochloride salt allowing it to vaporize at a lower temperature. Freebase differs from crack which is a mixture of cocaine hydrochloride and sodium bicarbonate. Both are highly potent!

Cocaine Mechanism • Produces its effect by • Competitive blockade of dopamine reuptake via the dopamine transporter. • Blocks reuptake of noradrenaline and serotonin. • Can also block the initiation and conduction of nerve impulses causing a local anesthetic effect.

Cocaine • Has a particular effect on the “pleasure pathway” mediated by dopamine. • In animal experiments, animals will almost uniformly choose cocaine over food or sex. • If given unlimited access, they will continue to dose themselves until they die from exhaustion.

Cocaine Intoxication C. 2 or more of the following: ■ Tachycardia and bradycardia ■ Pupilary dilatation ■ Elevated or decreased blood pressure ■ Perspiration or chills ■ Nausea or vomiting ■ Weight loss ■ Psychomotor agitation/retardation Muscular weakness, respiratory depression, chest pain or arrhythmias ■ Confusion, seizures, dyskinesias, dystonias, or coma ■ • DSM 5 Criteria • A. Recent use of cocaine • B. Clinically significant problematic behavioral or psychological changes ■ ■ D. Not due to a general medical condition.

Cocaine Intoxication • Remember… • • Cocaine activates the “fight or flight” system Therefore, you would expect to see a sympathetic nervous system stimulation: • • Increased HR and BP Pupilary dilatation Increased respiratory rate Etc…

Cocaine Overdose • Delirium and tactile • hallucinations are classic. Other bad consequences: • Seizure • Hyperthermia • Sudden death (cardiac • or vascular) Stroke

Cocaine Withdrawal • DSM 5 Criteria: • • ■ A. Cessation or reduction in cocaine use B. Dysphoric mood and 2 or more of the following: • Fatigue • Vivid, unpleasant dreams • Insomnia or hypersomnia • Psychomotor agitation/retardation. ■ ■ ■ C. Impairment from B symptoms D. Symptoms not due to a general medical condition. Withdrawal peaks in a few days, but can persist for months. ■ Suicidal ideation is common. Treatment is symptomatic. Benzos sometimes used.

Amphetamines • • • Speed Bennies Black beauties Copilots Crank Dexies Eye openers Meth E, Adam, Love drug (Ecstasy)

Amphetamines • First synthesized by German chemist L. Edeleano in 1887. • First marketed as benzedrine to treat nasal congestion. • Subsequently used to treat narcolepsy and ADHD. • Use for its stimulant properties increased dramatically during WWII when it was distributed by the ARMY to soldiers.

Amphetamines • • Amphetamines are a class of drugs that are related by chemical structure. All amphetamines are variations on the chemical structure of amphetamine. Some variants such as cathinone or ephedrine have only minor changes. Others, such as MDMA, have major substitutions.

Amphetamines • Traditional amphetamines produce their effect via several mechanisms: • • • They cause release of noradrenaline and dopamine from presynaptic neurons. They prevent reuptake of noradrenaline and dopamine by the presynaptic neuron. They act as monoamine oxidase inhibitors, thereby preventing degradation of the released neurotransmitters.

Amphetamines • Designer amphetamines result in the release of serotonin, in addition to the release of dopamine and noradrenaline.

Amphetamine effects • • Similar to cocaine intoxication: • • • Increased alertness Decreased need for sleep Decreased appetite Feelings of euphoria and self-confidence (to the point of aggression) Sympathetic activation. May present with delirium, psychosis, or mood disorder.

Amphetamine Intoxication • DSM 5 Criteria C. 2 or more of the following: ■ • A. Recent use of amphetamine. • B. Clinically significant problematic behavioral or psychological changes Tachycardia and bradycardia ■ Pupilary dilatation ■ Elevated or decreased blood pressure ■ Perspiration or chills ■ Nausea or vomiting ■ Weight loss ■ Psychomotor agitation/retardation Muscular weakness, respiratory depression, chest pain or arrhythmias ■ Confusion, seizures, dyskinesias, dystonias, or coma ■ ■ ■ D. Not due to a general medical condition.

MDMA - Ecstasy • MDMA was first synthesized in the 1890 s • Patented by Merck pharmaceuticals on December 24, 1912. • In the 1970’s, MDMA began to be used in psychotherapy as a tool to help patients “open up. ”

Ecstasy Effects • In addition to causing the previously described amphetamine effects, MDMA produces the following: • • Increased emotional openness Euphoria “a sense that all is right in the world” Increased intrapersonal insight

Ecstasy Effects • After the initial peak which lasts 3 -4 hours, users report an “afterglow. ” • Adverse effects from MDMA are often due to adulterants or serotonin depletion. • Long term use has been shown to increase incidence of depression due to serotonin depletion. • Studies suggest MDMA is neurotoxic.

MDMA Toxicity • A – Normal Monkey B – High dose MDMA

Crystal Meth • Basically a solid, “rock” form of amphetamine. • The methyl in “meth” makes the molecule more fat soluble. • More fat soluble = more blood-brain barrier penetration. • More penetration & smoking = addictive!

Bath Salts: Synthetic Cathinones • Beta-Ketone • • Amphetamines. Amphetamine-like properties with serotonin like properties. Anecdotal zombie-like behavior

Amphetamine Withdrawal • DSM 5 Criteria: • • ■ A. Cessation of reduction in amphetamine use B. Dysphoric mood and 2 or more of the following: • Fatigue • Vivid, unpleasant dreams • Insomnia or hypersomnia • Psychomotor agitation/retardation. ■ ■ C. Impairment from B symptoms D. Symptoms not due to a general medical condition. Withdrawal peaks in 2 -4 days and resolves in one week. ■ Depression is the most severe symptom and can be associated with suicidal ideation.

Phencyclidine (PCP) • PCP is a dissociative • • anesthetic with hallucinogenic effects. First synthesized in 1926. Parke-Davis began investigating PCP for use as a human anesthetic in the 1950’s.

PCP History • 1957: PCP is tested for the first time on 64 human subjects. • Troublesome side effects such as hallucinations, delirium, mania, and disorientation are noted. • 1963 -65: PCP is used as a anesthetic in humans, but is soon discontinued due to side effects.

PCP Mechanism • PCP functions as an antagonist at NMDA subtype of glutamate receptors. • Interestingly, NMDA receptor hypofunction has been implicated in the pathophysiology of schizophrenia. • PCP is also believed to activate dopaminergic neurons.

PCP intoxication • Effects of PCP are dose related: • • • Low dose (1 -5 mg): • CNS depressant causing nystagmus, blurred vision, and incoordination. Moderate dose (5 -15 mg): • hypertension, dysarthria, ataxia, increased muscle tone, hyperactive reflexes, and sweating. High doses (20 mg +): • fever, rhabdomyalosis, renal failure, seizure, depressed breathing, death.

PCP Intoxication • Famous for causing hallucinations and bizarre, sometimes violent behavior. • People may cause severe bodily injury secondary to the absence of pain produced by PCP’s anesthetic effect. • Effects last 3 -6 hours, but may persist for several days.

PCP Intoxication ■ • DSM 5 Criteria Vertical or horizontal nystagmus Hypertension or tachycardia ■ Numbness or diminished response to pain ■ Ataxia ■ Dysarthria ■ Muscle rigidity ■ Psychomotor agitation ■ Hyperacusis Confusion, seizures, or coma ■ • A. Recent use of ■ phencyclidine. • B. Clinically significant problematic behavioral or psychological changes C. 2 or more of the following: ■ ■ D. Not due to a general medical condition.

PCP Intoxication Treatment • Isolate the patient in a nonstimulating environment. • Wait for PCP to clear. • Urine acidification may increase clearance. • Use benzodiazepines for agitation. • Antipsychotics can worsen the psychosis. • May need to physically restrain the patient.

Ketamine (Special K, Vitamin K, K, Kit Kat) • A dissociative anesthetic. • The PCP of the year 2000. • Can be snorted, eaten, or injected. • Can cause auditory and visual hallucinations. • Causes feeling of dissociation. • Can cause profound respiratory depression.

Hallucinogens • Acid, trips, blotters • Shrooms, Magic • • mushrooms, Sacred Mushrooms, Teonancatl Peyote, buttons, mescalitos DMT

Hallucinogens • A broad category of drugs including: • • • d-lysergic acid diethylamide (LSD) Psilocybin Mescaline 5 -Me. O-DMT Ibogaine

Ergot Poisonings • • • Ergot is the common name for a fungus that grows on rye. Ergot alkaloids contain lysergic acid. It is speculated that many of the witch and werewolf hunts in medieval Europe may have been fueled by ergot poisoning.

LSD • 1938: Albert Hoffman synthesizes LSD in Basel, Switzerland. • Apr. 16, 1943: Hoffman accidentally experiences LSD and describes his 2 hour experience as “an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopelike play of colors. "

LSD History • Apr. 19, 1943: Hoffmann intentionally ingests 250 • • ug of LSD, rides home on his bicycle, and has a horrible trip. 1951: CIA begins experimenting with LSD. 1955: Aldous Huxley first takes LSD. 1959: Allen Ginsburg first takes LSD. 1963: Timothy Leary is fired from his teaching position at Harvard for his increasing interest and outspokeness about psychedelic use.

Hallucinogen Mechanism • Believed to work by acting as a serotonin receptor agonist. • LSD is active at 50 mcg

Hallucinogen Experience • Characterized by the following: • • • Changes in thought, feeling, and perception. Visual distortions and illusions are common. Body image, space, time perception is altered. Emotions become unusually intense. Suggestibility increases tremendously. Increased heart rate, pupillary dilatation, tachypnea occur.

DSM 5 Criteria • A. Recent use of a hallucinogen • B. Clinically significant problematic behavioral or psychological changes • C. Perceptual changes occurring in a state of full wakefulness and alertness. ■ Two or more of the following: ■ ■ Pupilary dilatation ■ Tachycardia ■ Sweating ■ Palpitations ■ Blurred vision ■ Tremors ■ Incoordination D. Symptoms not due to a general medical condition or other mental disorder.

Hallucinogen Adverse Effects • Hallucinogen hallucinosis – AKA Bad Trip • • • DSM 5 – Hallucinogen Persisting Perception D/O Resembles an acute paranoid or acute anxiety reaction. Symptoms may include: • • • panic depression confusion fear of insanity impaired reality testing.

Treating a Bad Trip • Reassure, reassure, • • • reassure. Benzodiazepines are a helpful adjuvant. Antipsychotics should be used as a last resort. Symptoms resolve when drug clears.

Flashbacks • Flashback: a transitory recurrence of perceptual and emotional changes originally caused by the drug • Have been explained as a post-traumatic reaction. • More likely to occur at times of fatigue, stress, or when under the influence of other drugs.

Other Stuff • • How long? • • • LSD, mescaline: 6 -10 hours Psilocybin: 2 -4 hours DOM: 24 hours Individuals with personal or family hx of psychiatric disorders are more likely to have a prolonged reaction to a hallucinogen.

Marijuana • Official genus: • Cannabis • Species • Sativa, Indica, Ruderalis • Known as: • Weed, Ganja, Bud, Grass, Loco weed, Reefer, Mary J, Herb, Pot

Marijuana • The key psychoactive ingredient in cannabis is: • delta-9 tetrahydrocannabinol • Aka THC • There are numerous other active compounds

Other Cannabinoids cannabigerolic acid cannabichromene cannabichromenic acid cannabicyclol (aka cannabipinol) cannabicyclolic acid cannabicitran cannabielsoic acids A and B cannabinolic acid (neutral cannabinoid) cannabichromanon cannabifuran dehydrocannabifuran 2 -oxo-[delta 3]-tetrahydrocannabinol cannabigerol monomethyl ether cannabidiol monomethyl ether cannabinol methyl ether propylcannabidiol (aka cannabidivarol & cannabidivarin) propylcannabinol (aka cannabivarol & cannabivarin) propyl-[delta 1]-THC (aka [delta 1]-tetrahydrocannabivarol & tetrahydrocannabivarin) propylcannabigerol propylcannabicyclol propylcannabichromene methylcannabidiol (aka cannabidiorcol) methylcannabinol (aka cannabiorcol) methyl-[delta 1]-THC (aka [delta 1]-tetrahydrocannabiorcol) [delta 1]-tetrahydrocannabivarolic acid

Marijuana • Cannabinoids are present in their highest concentrations in the mature female flowers or “buds. ” • The potent trichomes are also known as crystals.

Marijuana - Methods of Preparation • Dried Marijuana • Hashish • Kief • Hash Oil

Marijuana - Methods of Preparation Kief Hashish

Marijuana – Methods of Ingestion • Inhaled via pipe, bong, vaporizer, joint, or blunt. • Eaten in brownies, cakes, tea, etc. • THC is lipophilic.

Marijuana Effects • Psychoactive • Feelings of euphoria, wellbeing, relaxation. • Perceived enhancement of music or comedy. • Perceived effects on memory. • Paranoia or anxiety in some cases. • Physiological • Decreased intraocular pressure, increased conjunctival blood flow, increased heart rate, muscle relaxation.

Cannabis Intoxication DSM 5 Criteria • A. Recent use of a cannabis • B. Clinically significant problematic behavioral or psychological changes • C. Two or more of the following within 2 hours of use: ■ ■ 1. Conjunctival injection ■ Increased appetite ■ Dry Mouth ■ Tachycardia D. Symptoms not due to a general medical condition or other mental disorder.

Marijuana – How Does it Do it? • Endogenous Cannabinoid System • We have cannabinoid receptors (CB 1, CB 2). • We also have endogenous cannabinoids. • Anandamide was the first identified. • The system has been implicated in influencing: • Vision, memory, pain, reproduction, and inflammation • High concentrations of receptors are located in various CNS structures.

Cannabis Withdrawal • • A. Cessation of • cannabis use which has been heavy and prolonged B. Three or more of the following within one week of cessation: • Irritability, anger, aggression • Nervousness or anxiety • Sleep difficulty Decreased appetite/weight loss • Restelessness • Depressed Mood • Abdominal pain, tremors, sweating, chills, headache

Cannabis Withdrawal • C. Signs or symptoms in B. cause distress or impairment on social, occupation, or other important areas of functioning ■ D. Signs or symptoms are not attributable to a medical condition, etc.

K 2 aka Spice • A synthetic cannabinoid added to incense mixtures and smoked. • It has approximately 10 times more affinity for the cannabinoid receptor than THC. • Causes hallucinations, aggression, and profound thought disorganization.

Alcohol, Sedatives, & Hypnotics • Drug types: • Benzodiazepines: • Diazepam, flurazepam, lorazepam, alprazolam, etc • Barbiturates: Secobarbital, pentobarbital

Alcohol Facts • Beer is the 3 rd most consumed beverage. • Historically, alcohol was at times consumed rather than water to avoid water born diseases.

Sedative/Hypnotic Mechanism • GABA • The major inhibitory neurotransmitter • Receptor has binding sites for: • Benzodiazepines • Barbiturates • Picrotoxin • Steroids • Ethanol

Mechanism of Action • Alcohol, benzos, and barbs work by increasing the affinity of the receptor for its own neurotransmitter. • This mechanism suggests that the human body may produce endogenous benzos and barbs. • Endogenous benzos and “endozepines” have been identified.

Intoxication • • Behavioral disinhibition, analgesia, relaxation (0. 02 -0. 09) Slurred speech, nystagmus, drowsiness (0. 10. 3) Emotional volatility, confusion, blackouts (. 3 -. 4) Decreased respiratory drive, coma, death (>. 4)

Intoxication DSM 5 Criteria • A. Recent use of a sedative, hypnotic, or anxiolytic • B. Clinically significant problematic behavioral or psychological changes ■ C. One or more of the following: Slurred speech Unsteady Gait ■ Nystagmus ■ Impaired attention ■ Stupor or coma ■ Incoordination ■ ■ ■ D. Symptoms not due to a general medical condition or other mental disorder.

Withdrawal • Potentially life threatening! • Severity varies according to dose and duration of use. • Must watch patient for: • • Autonomic hyperactivity Tremor Seizures Psychosis

Sedative Withdrawal • DSM 5 Criteria: • A. Cessation of, or reduction in sedative use that has been heavy and prolonged. • B. 2 or more of the following within several hours to a few days after A: • Autonomic hyperactivity • Increased hand tremor • Insomnia • Psychomotor agitation • Nausea and vomiting • Transient tactile, visual, or auditory hallucinations or illusions • Anxiety • Generalized seizures ■ ■ ■ C. Impairment from B symptoms D. Symptoms not due to a general medical condition. Psychotic symptoms commonly begin on days 3 -8.

Sedative Withdrawal Treatment • Treatment of sedative withdrawal usually entails starting benzodiazepines ATC and tapering slowly. • Carbamazepine has been shown to decrease risk of seizure in patients. • Frequent vital sign checks a must! • In cases of overdose, give flumenazil.

Alcohol Screening • • CAGE – a good tool • Explore more if ‘yes’ to 2 or more Screen for dementia if long term dependence suspected.

Alcohol Dependence Conceptualization • Type 1 • • Onset after 25 yo Low degree of alcohol seeking behavior or related fighting Psychological dependence with mixed fear and guilt Low novelty seeking, high risk aversion

Alcohol Dependence Conceptualization • Type 2 • • Occurs before age 25 High alcohol seeking behavior and fighting Infrequent guilt and fear Low harm avoidance, high thrill seeking