Drug Education Exam 3

Life of a heroin user

-3-4 injections needed daily to prevent withdrawal - expensive habit (cost of drugs and paraphernalia) - risk of OD due to variable potency of diff batches - health problems associated with injection habit (skin infections, blood-borne infections, masking of early symptoms of illness) - some users "mature out"

Physiological effects of nicotine on various organ systems

-blood (increased clotting tendency) - lungs - muscular -GI - joints - CNS - heart - endocrine

Opioid withdrawal methadone detoxification management

- 20mg loading dose - 5mg po prn q 3hr - not to exceed 60mg in 24hr - divide stabilization dose into twice daily - decrease by 10-20% of stabilization dose per day to zero Note: methadone can be used for withdrawal management or maintenance purposes (aka for detox and to keep patients on stable dose). *If take depressant on methadone, you can OD*

Nicotine absorption and metabolism

- 90% of inhaled nicotine is absorbed - 80-90% is deactivated in the liver and then excreted via the kidneys - use of nicotine increases the activity of liver enzymes responsible for nicotine deactivation (contributes to tolerance)

Suboxone (generic name)

- Combo of buprenrophine sublingual form - Types of doses: 2mg Bup/0.5mg naloxone, 8mg Bup/2 mg Naloxone - Target dose is 8-16 mg per day

Sinsemilla

- Consists of dried flowering tops and plants with pistillate flowers (female plants) - male plants are removed form the fields before the female plants are pollinated - female plants don't put their energy into seed production, thus increasing their potency - average THC content of sinsemilla samples is about 7-12%.

History of Cannabis policy in CAN

- Since 1908 Opium Act, CAN has a strict drug control policy - for much of the 20th century Canada's illicit drug policy has been one of the most punitive drug control systems in the world

Cognitive effects of marijuana

- acute administration to INFREQUENT users distrupts cognitive performance: slowed cognitive processing, impaired short-term memory, impaired inhibitory control, loss of sustained concentration or vigilance, impaired visuospatial processing. - acute administration to FREQUENT users: causes less dramatic effects, implying they are tolerant to some (but not all) cognitive effects. Slowed cognitive processing, impairment during certain workplace tasks and the operation of machinery and automobiles can have significant effects - LONG-TERM cognitive functioning are more difficult to predict. Studies have had divergent findings and interpretations. Current evidence suggests that after abstaining for more than a month, regular marijuana use produces few effects on cognition. Additional (and better) research may change current thinking.

Abuse potential of marijuana

- both humans and animals will self-administer the drug - marijuana cigarettes with higher THC content are preferred - oral THC does not have high abuse potential likely due to its diff time course (less rapid onset usually associated w/ reduced risk of abuse)

Bhang

- consists of the remainder of the Cannabis plant after the top has been picked - plant material is dried, ground into a powder and mixed into drinks or candies. - rare in CAN but equivalent to low-grade marijuana consisting of leaves - Average THC content of less than 1%

Nicotine dependence

- debate continues despite scientific reports that cigarettes and other forms of tobacco are addicting. Nicotine is the drug in tobacco that causes addiction. - processes that determine tobacco addiction are similar to those that determine addiction to drugs like heroin and cocaine. - PHARMACOLOGY: stimulates reward centre (in most cases it is a function of suppressing your withdrawal symptoms) - FUNCTION: weight control, coping with negative affect/stress, cognitive enhancement. - SOCIAL FACTORS: friends, habit, context.

Study to assess long-term opioid maintenance effectiveness (SALOME)

- diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available because of a risk of overdoses and seizures. - clinical trial to test the hypothesis that hydromorphone (Dilaudid) is as good as diacetylmorphine for IV heroin replacement. - this and NAOMI projects are the only heroin maintenance programs to take place in N. America. - in 2010 the Vancouver team began receiving applications from interested participants. The 4 year trial will provide 322 research participants with heroin or hydromorphone. Researchers had planned for the SALOME study to also take place in Montreal but Quebec provincial authorities refused to fund SALOME. Therefore it will proceed in Vancouver alone.

Peyote

- from Aztec peyotl - small, spineless, carrot-shaped cactus, Lophophora williamsii Lemaire--> mostly subterranean, with only the pincushion-like top appearing above ground but entire plant is psychoactive. Buttons on plant contain mescaline - Long pre-Columbian history of use among Mexican Indians, who used the plan ceremonially (not illegal under confines of religion) - Arthur Heffter isolated several alkaloids from peyote and showed that Mescaline was the primary psychoactive agent found in peyote - Peyote cult moved north and became widely established among Indians of the plans by the late 19th century--> Native American church is an amalgamation of Christianity and traditional beliefs and practices of Native Americans, with peyote use incorporated into its ceremonies. USE: in religious ceremonies, as treatment for illness, worn as a protective amulet. CURRENT LAWS: vary from region to region for its use of peyote as a sacrament - although mescaline is a schedule 3 drug, peyote is specifically exempt

Ayahuasca "Vine of the Soul"

- from the Quechuan language of the Amazon region--> name for the vine Banisteriopsis caapi. Name for the brew made from the vine - Brew commonly combines Banisteriopsis, which contains harmaline with leaves of another plant containing DMT--> presence of harmaline allows oral DMT to have psychoactive effects

Amphetamine Derivatives

- group of synthetic hallucinogens chemically related to amphetamines. Due to chemical structure, they have few stimulant effects and act much more like mescaline - Ex. DOM, MDA and other "designer drugs", MDMA (Ecstasy) - Note: some evidence suggests that ecstasy may be neurotoxic, affecting serotonin neurons in the brain

Toxicity Potential of Cannabis

- growing evidence that average content of THC in cannabis is increasing - negative effects of cannabis use presumably related to THC content - Cannabidiol, another constituent in cannabis, is interesting b/c rather than producing psychoactive effects it produces anxiolytic and antipsychotic effects: potential to offset some of the adverse and negative effects of THC, variability in the cannabidiol content, exposure to cannabis with a higher THC content or low cannabidiol content might be associated with greater negative consequences.

Methadone pharmacology

- half life: 24-36 hours - absorbed within minutes - peark serum levels: 2-4 hours - side effects: constipation, nausea, sweats, impotence, menstrual irregularities, fatigue - excessive methadone dosages leads to sedation, lethargy, respiratory depression DOSAGES: start at 15-20 mg ** lethal dosage=70mg in non-tolerant individuals - optimal dosage: 60-100 mg - dosage adjustments daily during stabilization and every 5 days - withdrawal symptoms worst at end of taper

LSD Adverse Rxns

- impossible to determine true incidence of adverse rxns--> some bad rxns may be due to impurities in street LSD and/or preexisting psychological conditions in the user - panic rxns - flashbacks: recurrence of symptoms weeks or months after an individual has taken LSD. Rare, variable, and unpredictable in occurrence. Hallucinogen persisting perception disorder

Synthetic Cannabis

- new generation of synthetic cannabinoid agonists has been reported to be used recreationally - products are marketed as natural herbal incense or potpourri under various brand names such as "spice" or "K2" and have been sold legally in "head shops" convenience stores and through the internet to those seeking the "marijuanalike high" - may cause negative effects on human health

Misconceptions and preconceptions of drug use

- not all users experience euphoria from initial dose - tolerance to negative effects may develop more rapidly than tolerance to positive effects - withdrawal is often similar to a mild case of the intestinal flu - ppl usually don't become dependent after 1 dose - Current users: approx 1 million opioid dependent Americans and 2-3x that many occasional heroin users. Across CAN, heroin is the predominant drug of abuse in IV drug users.

Heroin-assisted treatment (HAT)

- patients are prescribed pharmaceutical-quality heroin (diacetylmorphine) in specialized clinics, is 1 available therapeutic option for chronic, long-term opioid infectors - was adopted in Switzerland after many drug users were not responding to traditional abstinence-based treatment programs.

Hawaiin Baby Woodrose

- seeds from the Hawaiin baby woodrose, Argyreia nervosa, have also been used recreationally. - seeds contain d-lysergic acid amide - outer coating of seeds contain toxic cyanogenic glycosides, which can make a user sick

Dimethyltryptamine (DMT)

- worldwide. Naturally occurring found in plants - the active agent in Cohoba snuff, used in some S. American and Caribbean Indian hunting rituals - usually snuffed, smoked or taken by injection. - Ineffective when taken orally - effects are very brief but tolerance does not develop to its psychological effects - it was first synthesized in 1931 by Canadian chemist Richard Manske and recognized for its psychoactive properties in 1956 - illegal to possess and sell - has never been widely used in CAN - in mammals, it is derived from the essential amino acid tryptophan during normal metabolism - listed as a schedule 3 drug

Compounds in tobacco

Tar: sticky substance. Amt varies from 12-16mg to 6mg. Last 3rd of cigarette contains 50% of tar. Prevents cilia from working. Increases carcinogens compounds to settle on tissue rather than being expelled.

Antagonist prescription opioids

naloxone and naltrexone

Early Medical Uses of Tobacco

- 1500's: recognition of the potential of tobacco grew - 1535: Jacques Cartier met Montreal natives using tobacco - Jean Nicot: made glowing reports. Plant genus Nicotiana and active ingredient named for him. - 16th and 17th centuries: viewed as having many positive medical uses but as having a negative reproductive effect - 1890s: Nicotine dropped from the US Pharmacopoeia

Heroin

- 2 acetyl groups added to morphine in the lab, creating diacetylmorphine. Given the brand name Heroin. Placed on the market in 1898 by Bayer - 3x as potent as morphine due to increased lipid solubility of the heroin mlcl (therefore has higher dependence rates) - acts like morphine except that it is more potent and acts more quickly - marketed as a non-habit-forming substitute for codeine (first used as cough suppressant)-- later linked to tolerance and dependence.

Catechol Hallucinogens

- 2nd group of phantastica, having psychological effects quite similar to those of the indole types, is based on a diff structure, that of the catechol nucleus - nucleus forms the basic structure of the catecholamine NTs (norepinephrine and dopamine)

Adverse health effects (notes)

- 85% of all lung cancers occurs in smokers - cancer causing agent in tobacco is not nicotine but aromatics such as benzo[a]pyrene which damage DNA causing cancerous mutations - every 11 minutes a Canadian dies from tobacco use ~47,000 ppl/year - 11,000 of these deaths are related to heart disease or stroke.

Marijuana mechanism of action

- Anandamide: endogenous substance isolated from brain tissue with marijuana-like effects. From ananda, Sanskrit for "bliss". - THC and other cannabinoids bind to 2 receptors: CB1 receptor and CB2 receptor. - CB1 receptor: found primarily in the brain but also unusually widespread throughout the body. Potential actions of cannabinoids are widespread. High density of CB1 receptors in specific brain regions- Basal ganglia (movement coordination), cerebellum (find body movement coordination), hippocampus (memory storage), cerebral cortex (higher cognitive functions), nucleus accumbens (reward)--> 4 things cannabis effects= cognition, memory (and learning), coordination (and movement) and cardiovascular systems - CB2 receptor: found mainly outside the brain in immune cells. Potential role of cannabinoids in the modulation of the immune system

Prevalence Rates of Cannabis use

- CAN Alc and drug use monitoring survey reports prevalence rates for cannabis is higher for males than females - the average age for initiation into cannabis use is 15-24 years - according to the United Nations Office on drugs and Crime, Cannabis is one of the most widely consumed illicit drug in the world - in CAN, presence of compassion clubs allows individuals to purchase strains of cannabis and a variety of cannabis products. - National average of cannabis use ~ 11% with about 8.5% for NB and 13.8% for BC. - Changes in prevalence rates: significant decreases in cannabis use is observed in the past year over a 5 year period. - most widely consumed illicit drug in the world (129-190 million ppl). Amphetamines ranked as 2nd most commonly used drug followed by cocaine, opiates and ecstacy

Tobacco History

- CAN has 3 major tobacco companies: 1. Imperial Tobacco Canada Limited (founded in 19th century in Montreal) 2. Rothmans, Benson and Hedges Incorporated 3. JTI- Macdonald Corporation - 90% of tobacco grown in CAN is produced in southwestern Ontario, near the towns of Delhi and Tilsonburg. - Chewing tobacco: in 19th century almost all tobacco produced in this form... Smoking did not surpass chewing until 1920s - Cigars: combo of chewing and smoking. Popularity peak in 1920. - Cigarettes: most popular form of tobacco. Native americans used thin reeds filled with tobacco. Factories appeared in 19th century. Habit spread with inexpensive machine-produced cigarettes. - 1930s and 40s: reports of link btwn smoking and cancer. In response, companies marketed filtered cigarettes with lowered tar and nicotine content. - 1964: reports state that smoking causes lung cancer in men. Tobacco sales began a decline that continued for 20 years.

LSD recreational use and Timothy Leary

- Experiments by psychologist Timothy Leary on Harvard grad students--> his research came under increasing criticism due to charges that he was being rigorous and using ethically questionable methods. - 1966: Leary started a religion, the League of Spiritual Discovery with LSD as a sacrament. Motto was "turn on, tune in and drop out" - Use peaked in 1967 and 1968 and then fell due to reports of problems associated with its use including "bad trips," prolonged psychotic rxns, worried about possible chromosome damage, self-injurious behavior and "flashbacks"

Additional effects of marijuana use

- Food intake: marijuana and oral THC significantly increase total daily calorie intake. Clinical use of cannabis-based drugs for appetite stimulation. Unclear if average chronic marijuana users are overweight. - Verbal behaviour: verbal exchanges decrease, nonverbal social interactions increase.

DOM and MDA

- MDA and others: group includes "designer drugs" that are not all specifically listed as controlled substances - DOM: 2,3-dimethyoxy-4-methylamphetamine. Earlier street name was STP ("serenity, tranquility, peace"). Effects similar to mescaline and LSD

OxyNeo

- March 2, 2012 oxycontin was taken off pharmacy shelves in CAN and replaced by oxyneo. - same active ingredient but in a new pill designed to be less soluble. Pill is harder and tougher so not as easy to crush. When placed in water, pill turns into a thick gel to prevent injecting it. Was supposed to be less-abusable designed by Purdue Pharmaceuticals. - first death from oxyneo occurred within first week of introduction.

LSD Experience

- Modifications of perceptions: visual images (shapes and patterns usually with intense colors and brightness), altered sense of time, changes in the perception of their bodies and alterations of auditory input, synesthesia ("mising of senses"- sounds may appear as visual images or visual pictures might alter in rhythm with music) - Enhanced emotionality: images may be perceived as beautiful and awe-inspiring or as intensely sad or frightening. - Form-constants: lattices, honeycomb or chessboard designs, cobwebs, tunnels, alley or cone shapes and spiral figures- may be combined with complex images - each trip is a unique experience - impact on creativity- unlikely to be enhanced successfully - unknown therapeutic usefulness

29th Century Romantic literature and the new science of psychology

- Napoleon's campaign to Egypt at the beginning of the 19th century increases the Romantic's acquaintance with hashish. - 1830s and 1840s, everyone who was anyone was using, thinking about using, or decrying the use of the mind-tickling agents such as opium and hashish - one of the earliest (1844) popular accounts of the use of hashish is in The Count of Monte Cristo by Alexander Dumas - well-known writers including Baudelaire, Gautier and Dumas wrote about the kind of effect to expect from hashish

OxyContin

- OxyContin: used for pain related to cancer (Purdue Pharma) - Oxycodon: active ingredient. - 10mg (white), 20mg (pink), 40mg (yellow), 80mg (green). - Slow release (SR) tablets remains in effect for 12 hours - contains more oxycodone than percodan or percocet. - designed to be taken orally but abusers chew tablets, crush and snort powder and dissolve in water for IV administration - effects similar to heroin

Opium and Heroin Supply, Distribution and Trafficking in Canada

- Poppies don't grow in CAN-- imported and distributed through illegal and criminal channels in South and Southwest Asia (primary supplies to CAN) - opium powder is openly sold throughout major cities such as Toronto and Vancouver and can be puchased for as little as $1/g-- a cheap unconventional high - maj source of illicit opioid use is available through prescription.

Methadone history

- W/D and psychotherapy unsuccessful - relapse related to craving - goal: rehabilitation not abstinence - morphine maintenance - methadone maintenance program: 107/120 retained dependent on methadone 3 years after program, 80-120 mg dose, heroine blocking effect

Opioid mechanism of action

- act on selective receptors in the brain - naturally occurring opioid-like products of the nervous system and endocrine glands activate brain opioid receptors 1. Enkephalins: morphine like NTs found in the brain and adrenals 2. Endorphins: morphine like NTs found in the brain and pituitary gland - natural and synthetic opioid drugs as well endogenous opioids act on multiple types of opioid receptors in the brain.

Nicotine withdrawal

- begins within a few hours - peaks in a few days - lasts 4 weeks - considerable individual variability - most ppl release within first week when withdrawal symptoms at their peak - symptoms: anxiety, inadequate sleep, irritability, impatience, difficulty concentrating, restlessness, cravings, hunger, GI problems, headaches, drowsiness.--> similarities with alcohol, opiate and cocaine withdrawal symptoms.

Hashish

- consists of pure resin that has been carefully removed from the surface of leaves and stems - may be less than pure depending on how carefully the resin has been separated from the plant material - average THC content of hashish ranges from 3-8%. A few batches have tested as high as 20% THC. - production methods: traditional production involves manual scraping of exuded resin from the plant. More efficient recent production method involves boiling the plants in alcohol and evaporating the resulting liquid down to thick, dark hash oil. Potency of hash oil varies but can contain more than 50% THC

The changing profile of opioid users

- high-risk street drug= heroin - increased prevalence rates of illicit opioid use in N. America for decades. Heroin does not account for this increase but prescription opioid analgesics (morphine, hydromorphone, oxycodone) do. - marked rise in non-medical use of drugs in CAN -2005: CAN ranked 1st in world for per capita consumption of dilaudid (hydromorphone), second for MS Contin (morphine) and oxycontin (oxycodone) and 3rd for vicodin (hydrocodone) - indication that both medical and non-medical uses precipitate opioid dependence and overdose - percentage of illicit opioid users entering methadone meaintenance treatment in TO currently using POs either with or without concurrent heroin use -prescription of opioids for pain treatment identified as contributing factor to opioid dependence and abuse - annual consumption of analgesic opioids increased substantially in CAN btwn 2001-2005--> oxycodone use increased by 230%, fentanyl by 159%, morphine by 28%. - heroin use has been small for the past decase (1% adults reported ever using heroin, 0.2% reported using in the past year). Although most associated with IV use, dependence can occur via any route that produces behavioural or physiological effects.

Psilocybin: "Magic Mushrooms"

- long history of use among natives in Mexico - Psilocybe mexicana is the most well-known psychoactive mushroom - primary active ingredient is the indole psilocybin. Dried muschooms are 0.2-0.5% psilocybin - effects are similar to LSD and mescaline and cross-tolerance exists among the three - effects depend on dose. Up to *4mg* causes relaxation and some body sensations. Higher doses cause perceptual and body-image changes with hallucinations in some individuals - sympathetic arousal symptoms. May be active after converted to psilocin. - Good Friday study (1962) by one of Timothy Leary's followers: seminary students were given psilocybin or a placebo 90 minutes before attending a religious service. Study looked at effect and magnitude of changes caused by the drug and at the durability of the changes - Researchers concluded that under certain circumstances, the drug enhances mystical or religious experiences - most current production is from local, amateur growers. - "Shrooms" might be consumed at a party in combo with alcohol - another potent commonly occurring psilocybin-containing muschroom, Psilocybe semilanceata is found in Atlantic provinces and BC - in CAN, spores such as Psilocybe cubensis can be readily purchased from suppliers through the internet - Mushroom spore kits are legal and are sold openly as possession of the spores themselves are not illegal -psilocybin and psilocin are illegal to possess and sell as they are listed as schedule 3 drugs in Canada's controlled drug and substance act.

Supply, Distribution and Trafficking of Marijuana

- marijuana is cultivated both indoors and outdoors through indoor. Indoor production sites more common due to larger yields of the THC levels and increased privacy to avoid law enforcement detection - According to the 2009 report on illicit drug situation in CAN by the Royal Canadian Mounted Police, amount of marijuana produced in CAN exceeded domestic demand resulting in organized crime producing it for export to foreign markets - Cultivation and production predominantly in BC, Ontario and Quebec - in 2009, CAN law enforcement seized a total of ~34,000 kg of marijuana and ~1.8 million marijuana plants. While majority of marijuana seized was domestically produced, the drug continued to be imported from Jamaica, US , Europe and Asia. - hash oil smuggled into CAN has historically originated from S. Asia countries like Afghanistan and Pakistan and continues to do so - *Jamaica has been the primary supplier of hash products to CAN* - Grow-ops worth $17 million and set by organized crime groups have been busted in Calgary area.

Cannabis (the plant)

- marijuana is the leaves from Cannabis plant. It is classified separately because its effects are varied and complex: sedation, pain relief, hallucinations (in large doses). Effects is produces in most users are sufficiently different from the effects of depressants, narcotics and hallucinogens to merit its separate classification. - Cannabis has 3 types: marijuana, hashish and hash oil. - Health CAN against marijuana, working to protect public safety while providing reasonable access for medical purposes.--> Marijuana medical access regulations 2001.

Physiological effects of nicotine

- mimics acetylcholine - first stimulates and then blocks certain receptor sites - causes the release of adrenaline and has an indirect sympathomimetic effect - symptoms of nicotine poisoning: low level (often experienced by beginning smokers) includes nausea, dizziness and general weakness. Higher-level includes tremors, convulsions, paralysis of breathing muscles, death. - CNS and circulatory system effects: increased HR and BP, increased oxygen need of the heart, decreased oxygen-carrying ability of blood which causes shortness of breath, increased platelet adhesiveness, increased electrical activity in the cortex. - Reduced hunger: inhibition of hunger contractions, increased blood sugar, deadening of taste buds.

Abuse of POs

- most popular POs are various brands of hydrocodone (vicodin and lortab) and oxycodone (OxyContin and Percocet) - Mostly taken orally but when used recreationally they can be snorted or injected - use far exceeds cocaine use but much lower than marijuana use - concern about the relatively high rates of non-medical use of opioids and their potential for toxic consequences when misused has led Health CAN the US FDA and drug manufacturers to take preventive measures.

Opioids

- naturally occurring substances derived from the opium poppy have a 6,000-year history of medical use - relieve pain and suffering - deliver pleasure and relief of anxiety--> long history of recreational use - papaver somniferum is an annual flowering plant that grows 3-4 ft high (probably originated from middle east)

Nicotinic acetylcholine receptors

- nicotine affects dopamine like cocaine and heroine. - Binding to acetylcholine receptor in the VTA results in a release of dopamine

Challenges to quit smoking

- nicotine is a strongly reinforcing drug - pack-a-day smoker puffs at least 50,000 times a year - six-month relapse rate from smoking cessation is extremely high (70-80%)

LSD

- not found in nature; is synthesized from alkaloids extracted from the ergot fungus Clavicips purpurea-->eating grain infected with this mold causes an illness called ergotism. During a famine, grain infected with the ergot fungus might be consumed instead of destroyed leading to outbreaks of ergotism - 1938: Synthesized by Dr. Albert Hofmann of Sandoz laboratories in Switzerland - 1943: Dr. Hofmann took a large dose and described its effects. - potency of the drug attracted attention- a very small dose produces effects. Would require 4000 times mescaline to produce same effect. - btwn 1950s and 1970s there was a tremendous amt of research preformed-- in psychotherapy to help patients bring up repressed memories and motives. Dr. Hofmann believed it was a valuable psychedelic tool and could be used to enhance humans' understanding of their place in nautre. - most research did not contribute much to understanding the effects of this drug -since 1975, research focuses on drug's action at the neural level.

Medical uses of Cannabis in CAN

- number of cannabis-based medicines are approved for use in CAN - oral form of synthetic THC known as dronabinol is marketed in the US and CAN as Marinol- indicated for treatment of severe nausea, vomiting associated with cancer chemotherapy and AIDS related to anorexia. - A buccal spray known as Sativex is marketed as an adjunctive agent for neuropathy for MS patients and as an adjunctive analgesic for cancer patients for pain relief. - Health CAN document info for Health Care Professionals: Cannabis (Marihuana, Marijuana) and the Cannabinoids - chemotherapy-induced nausea and vomiting (CINV) is most common adverse events associated with cancer treatment - use of cannabis/cannabinoids has been reported to provide a measure of relief - activation of cannabinoid CB1 and CB2 receptors, identified in areas of the brain stem associated with emetogenic control, may underlie in these purported effects. - antiemetic action through more than one mechanism including antagonism of 5-HT3 receptors - strong evidence that the endocannabinoid system plays an important role in the modulation of pain - elements of the endocannabinoid system found at supraspinal, spinal and peripheral levels of pain pathways - randomized, double-blind, placebo-controlled studies suggested oral THC (dronabinol, marinol) provided an analgesic effect in ppl with moderate to severe continuous pain caused by advanced cancer. - Sativex is approved as an adjunctive treatment for advanced cancer pain. - the Marijuana for medical purposes regulations allows use of dried marijuana in cancer patients experiencing severe pain - anecdotal reports have suggested that marijuana can alleviate symptoms of spasticity and provide relief and improvements in sleep for patients suffering from multiple sclerosis - while there are benefits for management of glaucoma, there have been no recommendations from the Canadian Opthalmological Society or the American Glaucoma Society - historical and anecdotal evidence for asthma - the centre for addiction and mental health (CAMH) does not encourage or promote cannabis use - CAMH recommends that cannabis possession can be considered as a civil violation

Supervised injection facility (Insite)

- nursing services and care for skin abscesses. - annual operating cost was $3 mill in 2007 - launched in 2003 in Vancouver

Cultivation of opium

- only available for collection for a few days of the plants life - use sharp, clawed tool to make shallow cuts into the unripe seedpods. The resinous substance that oozes from the cuts is scraped and collected. -Raw opium is the substance from which morphine is extracted and then heroin is derived **OPIUM, MORPHINE AND CODEINE= naturally occuring in seed (heroin is then manufactured from morphine)

Cannabis preparations

- primary psychoactive agent in Cannabis is DELTA-9-TETRAHYDROCANNABINOL (THC)--> is concentrated in the resin, most of which is in the flowering tops. Less is in the leaves, little is in the fibrous stalks. Psychoactive potency of Cannabis prep depends on the amount of resin present. - ~60 chemicals in cannabis plant but delta9 THC is the only pharmacologically active ingredient. - traditional prep in India correspond roughly to types available in CAN (Charas- known as hashish, Ganja- known as sinsemilla from Spanish sin semilla "without seeds", Bhang- powder that can be mixed into drinks or candies rare in CAN but it is similar to our low-grade marijuana. Also called "red oil of cannabis" or hashish oil. Liquid form of marijuana)

Behavioural effects of marijuana

- produces robust self-administration by human marijuana smokers and that marijuana self-administration is related to the THC content of the cigarettes. - Subjective effects include euphoria, "high", mellowness, hunger and stimulation. Peak effects occur within 5-10 minutes and last for ~2 hours. Oral THC has similar effects but a diff time course. Magnitude of effects is greater with increasing THC concentrations. Regular marijuana smokers can recognize the effects and distinguish btwn real and placebo marijuana cigarettes - Subjective effects of infrequent smokers: experiene similar but more intense effects compared with experienced smokers due to lower tolerance. At high THC concentrations may report negative effects such as mild paranoia and hallucinations

Pharmacology of Mescaline

- rapidly absorbed if taken orally - half-life 6 hours - Effects: low dose= primarily euphoric, high dose= full set of hallucinogenic effects - most mescaline is excreted unchanged - psychoeffective dose causes sympathetic arousal - LD50= 10-30x the dose needed to cause behavioural effects - tolerance develops more slowly to mescaline than to LSD - cross-tolerance btwn LSD and mescaline

Pharmacology of Opioids

- raw opium is ~10% morphine by weight and a smaller amt of codeine - with added acetyl groups, heroin can pass through the blood-brain barrier faster, making heroin more potent than morphine - opioid antagonists: drugs that block the action of opioids Ex. naloxone (Narcan) and nalorphine--> Effects: reverse depressed respiration from opioid overdose, precipitate withdrawal syndrome, prevent dependent individuals from experiencing a high from subsequent opioid use.

Compassion Clubs in CAN

- self-regulated and no federal standards under which they operate to produce and distribute marijuana - Health CAN in 2010 stated it does not license compassion clubs to possess, produce or distribute marijuana for medical purposes. Health CAN is the only organization that can supply individuals with seeds or dried marijuana for medicinal purposes. - operate outside of Canada's laws - purchase of marijuana through these clubs is subject to law enforcement measures

Nicotine behavioural effects

- smokers report it has both stimulant and calming effects - user expectation probably plays an important role in the effects - smokers are able to sustain their attention to a task requiring rapid processing of information from a computer screen much better if they are allowed to smoke before beginning. --> nicotine either produces beneficial effect on this task or prevents withdrawal symptoms during task.

Reefer Madness "Marijuana Madness"

- some researchers are collecting data that they claim shows that marijuana causes psychosis - some studies have found a correlation btwn marijuana use and psychotic symptoms - participants admitted to having at least 1 psychotic symptom - it is possible the ppl had psychotic symptoms prior to using marijuana - since marijuana users typically use other psychoactive drugs, it is difficult to disentangle the influence of other drug use on the psychotic symptoms - there is evidence that marijuana can increase the likelihood of psychotic episodes in individuals with a history of psychiatric problems

Opioid Withdrawal

- starts in 6-12 hours after last dose, peaks in 3 days, done in 5-7 days (acute withdrawal) and then months of protracted withdrawal.--> applies to all opioids except methadone which has a half life of 24-36 hours.

Typical smoker

- takes ~10 puffs on cigarette at intervals of about 30-60 seconds - each puff delivers small burst of nicotine to brain - smokes 1.5 packs (30 cigarettes) per day--> 300 puffs of nicotine per day

Contraindications of Cannabis Use

- the contraindications that apply to those considering using Sativex or Marinol also apply to the use of marijuana. - Marijuana is contraindicated in: any person under 18 yo, anyone who has history of hypersensitivity to any cannabinoid or to smoking, ppl with liver, kidney or cardiopulmonary disease or a history of this, psychiatric disorders, particularly schizophrenia, women of childbearing age not on a reliable contraceptive as well as those planning pregnancy, those who are pregnant or women who are breastfeeding, men intending to start a family, shouldn't use with other CNS depressants including alcohol, or with use of any other drugs (increases incidence of adverse effects).

Causes for concern of cannabis use

- the euphoric effect produced by cannabis is not as intense as that produced by other psychoactive drugs, such as cocaine or heroin - cannabis use possesses a dependency syndrome and withdrawal symptoms with cessation of frequent or high-potency use.

Smoke constituents reaching bloodstream factors (6)

- type of tobacco - presence/absence of a filter - effectiveness of filter - puffs/cigarette and dept of inhalation - proportion of cigarette smoked - manner of smoking

Cannabis history

- use goes back to 3rd millennium BCE - Earliest mention in chinese pharmacy book (2737 BC) - social use of the plant had spread to the muslim world and N. Africa by AD 1000. "Hashishiyya" religious cult carried ot political murders. Story of cult spread in works by Marco Polo (1299) and Boccaccio (1350s)- origin of the term assassin. Hashish use mentioned frequently in The Arabian Nights.

LDS Secret army/CIA Research

- various militaries experimented with LSD and other hallucinogens--> between 1950s and 1960s, hundreds of soldiers and civilians were unwittingly given doses of the drug. Subjects believed they were losing their minds. Some suffered psychiatric disorders and others had difficulties adjusting to their usual lives. - Army/CIA-sponsored research was poorly done and violated many ethical codes--> once knowledge of the activities become public, the US government was required to pay reparations exceeding hundreds of thousands of dollars to some subjects and their families. - CAN government funded research in 1950s and 1960s in collaboration with the CIA in mind control and behaviour modification - Project MK-ULTRA involved the investigation of US prisoners and CAN patients in N.American hospitals without their consent - btwn 1950-64, at Allen Memorial Institute at McGill University, patients were experimented with LSD and electroshock therapy without their consent.

Fentanyl

- ~100x stronger than morphine. Comes as a patch that is slow-release intended mainly to treat patients suffering cancer-related pain who have built up tolerance to other opioids. - comes in ug whereas other drugs comes in mg. (EXTREMELY POTENT) - associated with >100 deaths in Alberta alone in 2014

North American opiate medication initiative (NAOMI)

- ~75,000 and 125,000 ppl inject drugs in CAN, with cocaine and heroin being the favoured injectable substances - street available prescription analgesic opioids (hydromorphone and morphine) have been on the rise in the recent years as well as IV use of heroin in larger cities. - in 2006, randomized controlled trial with injectable heroin was conducted to evaluate the effectiveness of heroin assisted treatment in the CAN context, targeting those who did not respond to conventional treatment options. - Opioid agonist substitution therapy: illicit opioids are replaced with a legal one--> is the most effective treatment option currently available - oral methadone maintenance treatment (MMT): most common route of administration for substitution treatment. - in 2006, the NAOMI trail evaluated the feasibility and effectiveness of HAT in the Canadian context. Study targeted severely affected individuals who had not benefited from conventional treatments. Participants were randomly assigned to 3 groups: 1. a control group received oral methadone 2. an experimental group received prescription heroin 3. small group received injected hydromorphone (dilaudid). The hydromorphone group helped validate the reported use of illicit heroin beyond what is prescribed in the study. RESULTS: injectable diacetylmorphine maintenance was more effective than methadone maintenance in retaining participants in addiction treatment and reducing the use of illicit drugs and illegal activities. Diacetylmorphine maintenance therapy should be delivered ins settings where prompt medical interventions are available. Injection patients could not accurately discriminate btwn diacetylmorphine and hydromorphone. The researchers hypothesized that if hydromorphone proves to be as good as diacetylmorphine, participants could achieve the benefits of opioid injection maintenance without the emotional regulatory barriers presented by heroin maintenance. NAOMI investigators designed a study to test this hypothesis known as the study to assess longer-term opioid medication effectiveness (SALOME) clinical trial.

The opium wars

-1729: opium smoking outlawed in China but smuggling was widespread - British East India Company was involved in opium trade, legally in India and illicitly (but indirectly) in China - Pressure grew and eventually war broke out btwn the British and Chinese.

Morphine

-1806: active ingredient in opium isolated (10x as potent as opium). Named morphium (after Morpheus, the god of dreams) - 1832: another alkaloid of opium discovered. Named codeine from the Greek word for "poppy head". - medically useful characteristics: clinically useful, pure chemical, known potency. - use spread due to 2 developments: 1. 1853: hypodermic syringe allowed delivery of morphine directly into the blood 2. widespread use during war provided relief from pain and dysentery. -- dependence later called "soldier's disease" or "army disease."

Smokeless Tobacco

-1970s: increased due to desire of method of tobacco use with lower risk of lung cancer - forms: moist snuff - benefits: less expensive, easier to use outdoors, more socially acceptable in some circumstances, less likely to cause lung cancer - snuff: during 18th century, smoking dimished and snuff became widespread. Perceived as a British product and American use declined after the Revolution. - Health and cosmetic concerns for smokeless tobacco: bad breath, spitting, disposal of quid, significanlty increased risk of dental disease and oral cancer, contains nitrosamines and other potent carcinogens, causes leukoplakia, nicotine absorbed through mucous membrane. Packages carry warning labels. - general decline in tobacco use in recent years, but increase in cigar use in the mid 1990s.

Cannabinoid chemicals (Pharmacology)

-Chemistry is complex and unique. Active agent contains no nitrogen and thus is not an alkaloid like other psychoactive plant materials - Cannabinoids are 66 chemicals unique to the Cannabis plant - Delta-9-tetrahydrocannabinol isolated and synthesized in 1964. Most pharmacologically active cannabinoid. May be several other active agents in Cannabis. - Smoked marijuana: THC is absorbed rapidly by the blood and travels to the brain and then the rest of the body. Within 30 minutes, most THC is gone from the brain. Peak psychological and cardiovascular effects occur together within 5-10 minutes. - Oral THC: absorbed more slowly and the liver transforms it into 11-hydroxy-delta-9-THC. Less THC reaches the brain. Peak effects occur about 90 minutes following ingestion. - Metabolites have diff half-lives: after 1 week, 25-30% of THC and its metabolites might remain in the body. 2-3 weeks may be required to completely eliminate a large dose of THC and its metabolites. - High lipid solubility of THC and its metabolites. Selectively taken up and stored in fatty tissue, to be released slowly. No easy way to monitor THC and metabolite levels and relate them to effects. Long-lasting low concentrations of THC and metabolites may have effects of the brain and other organs that have not yet been determined.

Abuse and dependence on cannabis

-DSM-5: no listing of cannabis withdrawal but research suggests an abstinence syndrome does exist--> symptoms: negative mood states- anxiety, irritability, disrupted sleep, decreased food intake, aggressive behavior (in some cases), begins about 1 day after the last dose, lasts 4-12 days. (not life threatening but unpleasant) - relative to other drugs of abuse, many ppl perceive marijuana to be an innocuous drug with limited abuse potential - tolerance to many marijuana effects develops after regular use of high levels. May not develop uniformly to all effects - Marijuana has an abuse potential - A significant minority of current marijuana users may be abusing or dependent on the drug

Phantastica

-Hallucinogens can be classified by: 1. chemical structure 2. known pharmacological properties 3. how much loss of awareness they cause 4. how dangerous they are - 2 major groups 1. Classical phantastica: alter perceptions while allowing the user to remain in communication with the present world 2. Deliriants: produce more mental confusion, greater clouding of consciousness and a loss of touch with reality.

Smoking and Pregnancy

-Increased risk of miscarriage, low birth weight and SIDS - later effects on physical and intellectual development (neurological problems, problems w/ certain reading and math skills, hyperactivity - effects are of the same type and magnitude as those reported for "crack babies"

Suboxone abuse potential

-buprenorphine has moderate bioavailability - naloxone has poor bioavailability. Buprenorphine opioid effects predominates. Naloxone does nto precipitate opioid withdrawal in the opioid dependent individual. - crushed and injected--> naloxone via injection has good bioavailability, naloxone effect predominates. Can precipitate withdrawal**

Mescaline

-isolated and synthesized by 1918 - peyote includes many other psychoactive alkaloids but mescaline has been identified as primarily responsible for the visual effects - users may experience bad trips as well as nausea and physical discomfort - San Pedro cactus: another mescaline-containing cactus, Trichocereus pachanoi, has also been used for thousands of years, but its recreational use is limited by frequent adverse side effects

Passive Smoking (Secondhand smoke)

-non-smokers inhaling from environment - death of Heather Crowe in Ottawa from occupational exposure to second hand smoke provoked the smoke free Ontario act. - Components of environmental tobacco smoke 1. side stream smoke: smoke rising from the ash of a cigarette. Is higher in carcinogens. 2. Mainstream smoke: the smoke inhaled/exhaled by the smoker - health effects difficult to define but include: lung cancer, cardiovascular disease and other adverse health effects.

Treating tobacco addiction

1. Buproprion SR 2. Nicotine gum 3. Nicotine inhaler 4. Nicotine lozenge 5. Nicotine patch 6. Nicotine mouth spray 7. Varenicline (blocks nicotine-R but still triggers dopamine release) (may combine meds)

3 types of Cannabis

1. Cannabis sativa: originated in Asia but now grown worldwide. Grown primarily for its fibers, from which help rope is made. Grows as a weed in the US and CAN. A lanky plant up to 18 feet high. 2. Cannabis indica: grown for its psychoactive resins. Cultivated in many areas around the world. A compact plant 2-3ft high. Potency varies depending on plant genetics and environmental conditions. 3. Cannabis ruderalis: grown primarily in Russia.

How to tamper with new oxyneo (from internet)

1. microwave pill for 5 minutes 2. put in freezer for 1:30 3. grind pill into fine powder with tool. The finer the powder will destroy the time release more effectively 4. put onto microwave-safe plate 5. microwave for 4:30-5 minutes 6. as soon as you start to see the pill turn into a brown gunk pull it out (sometimes doesn't turn brown) 7.put into freezer for 5-10 minutes 8. scrape the crusted brown oxy and snort

Nicotine pharmacology (7)

A naturally occurring liquid alkaloid that is colorless and volatile. Water and lipid soluble, rapid absorption across pulomnary alveoli (heart brain and other organs), readily absorbed across mouth and nose (smokeless tobacco, cigars, pipe smoke), plasma half life of two hours. Tolerance and dependence develop quickly. Highly toxic. Lethal dose=60 mg but typically not delivered fast enough or in a high enough dose to be lethal. A cigar contains twice the lethal dose of nicotine.

Toxicity Potential

ACUTE PHYSIOLOGICAL EFFECTS: increased heart rate, possibly risky for someone with preexisting cardiovascular disease. No human OD deaths have been reported. -Driving ability: 4.8% CAN drove within 2 hours of cannabis use at least once in the past year. Research findings mixed--> lab studies of computer-controlled driving stimulations shows that marijuana produces significant impairment. Epidemiological studies show little evidence that drivers who use marijuana alone are more likely to cause an accident. Effects may be more severe in infrequent users. CHRONIC - lung exposure from marijuana smoking impairs air flow in and our of the lungs but long-term implications for health are unclear. - Marijuana smoke contains many but not all the chemicals found in tobacco smoke (tar, carbon monoxide, hydrogen cyanide, nitrosamines, benzopyrene (carcinogen found in higher levels in marijuana cigarettes than in tobacco cigarettes). - marijuana cigarettes are not filtered. - smoking behaviour among regular marijuana users: smoke fewer marijuana cigarettes than tobacco users smoke standard cigarettes. Hold smoke deep in their lungs longer than do cigarette smokers. - no direct evidence that marijuana smoking causes lung cancer-- more time may be required to show the link PANIC - major behavioural problem associated with acute marijuana intoxication is the panic rxn: characterized by fear of loss of control and fear that things won't return to normal. Some ppl require a medical sedative or tranquilizer but the best method to remind a person everything will go back to normal is a "talking down". REPRODUCTIVE EFFECTS - reduced testosterone levels in men - diminished sperm counts and abnormal sperm in men - a growing number of studies show that marijuana use by pregnant mothers does not appear to be associated with low birth weight or premature birth but amts of marijuana used by the women in these studies were relatively low IMMUNE SYSTEM EFFECTS - findings have been mixed--> some evidence that marijuana use reduces immunity to infection - mortality data does not show a relationship btwn marijuana use and overall death rate AMOTIVATIONAL SYNDROME - concern about the effect of regular marijuana use on behaviour and motivation - lab data do not support the hypothesis that frequent marijuana smokers exhibit diminished motivation

Physiological effects of cannabis

CARDIOVASCULAR: increased heart rate occurs after smoking marijuana and ingesting oral THC. Time course differs substantially following the 2 diff methods of administration. Research findings on the effects of cannabinoids on blood pressure have been mixed. Cardiovascular risks of marijuana use haven't been shown in young, healthy users. Ppl with cardiovascular disease should probably avoid marijuana and oral THC due to effects on heart rate. PULMONARY: Bronchodilation is seen following acute exposure to marijuana. Heavy marijuana smoking over a long period could lead to clinically significant impairment of pulmonary function REDDENING OF THE EYES DRYNESS OF THE MOUTH AND THROAT

Causes of concern for opioids

DEPENDENCE POTENTIAL--> PHYSICAL DEPENDENCE: symptoms of withdrawal appear in sequence following the timing of the most recent dose and the individual's history of use. Opioid withdrawal is unpleasant but rarely life-threatening. Methadone (long-lasting synthetic opioid) produces withdrawal symptoms that appear later and are less severe than those from heroin. TOLERANCE: develops to most effects from both medical and recreational usage (higher doses needed to maintain effects). Cross-tolerance exists among all the opioids. Psychological processes play a key role in tolerance. Dependent individuals develop a conditioned reflex response to the stimuli associated with taking the drugs. Note: will not give you the same effect all the time-- when you get tolerant you don't get the good feeling anymore you are just running away from the withdrawal symptoms.

Physiological effects of Nicotine in non-tolerant and tolerant individuals

In non-tolerant individual: 200-300ug--> dizziness, headache, sweating, nausea, abdominal cramps, possibly vomiting and weakness. In smokers: symptoms abate as tolerance develops

Phantastica major groups

Indole hallucinogens= drugs that have the indole structure also found in serotonin ex. LSD, psilocybin Catechol hallucinogens= drugs that have the catechol nucleus that forms the basic structure of norepinephrine and dopamine. ex. mescaline, MDMA (Ecstasy)

Beneficial uses of opioids

PAIN RELIEF: reduces the emotional response to pain and diminishes the patient's awareness of, and response to, the aversive stimulus. Typically causes drowsiness but does not induce sleep TREATMENT OF INTESTINAL DISORDERS: Reduces colic and counteracts diarrhea and the resulting dehydration. Acts by decreasing the number of peristaltic contractions. An opium solution known as paregoric is still available for relief of diarrhea COUGH SUPPRESSANT: Codeine has long been used to reduce coughing (remains available in prescription cough meds). Nonprescription cough remedies contain the opioid analogue dextromethorphan (produces hallucinogenic effects at high doses)

Causes for concern: suboxone

PSYCHOLOGICAL DEPENDENCE: positive reinforcement (positive effects reliably follow use of the drug). Negative reinforcement (use of the drug removes withdrawal symptoms). Fast acting injectable opioids are most likely to lead to dependence. ACUTE TOXICITY: opioids depress respiratory centers in the brain (breathing becomes slower and shallower). Effects with alcohol are additive. Opioid overdose triad (coma, depressed respiration, pinpoint pupils). Clouding of consciousness. Occasionally, nausea and vomiting. Can be counteracted with naloxone. CHRONIC TOXICITY: is associated with injection method of use ex. infections and the spread of blood-borne diseases.

Terminology and Types of hallucinogens

Phantastica: drugs that create a world of fantasy in our minds Psychedelic: "mind-viewing," a term that controversially implies a beneficial, visionary type of effect. Psychotomimetic: "mimicking psychosis"- by producing hallucinations and some altered sense of reality, these drugs produce a state that could be described as psychotic. Entheogen: substances that create spiritual or religious experiences Entactogens: substances that enhance feelings of empathy Hallucinogens: a drug that produces profound alterations in perception, including unusual visual sensations and often changes in the perception of one's own body

Opioid use vs. withdrawal

USE: decreased BT and BP, warm/flushed skin, pupil constriction, constipation, decreased respiration,decreased sex drive, muscle relax, nods/stupor, analgesia, euphoria WITHDRAWAL: increased BT and BP, gooseflesh, tearing/runny nose, diarrhea, yawning, spontaneous orgasms, restlessness/twitching, insomnia, pain, depression/anxiety.

Hookah

large, ornate water pipes imported from Arab countries. Produce milder, water-filtered tobacco smoke.

Adverse Health Effects (main)

lung cancer cardiovascular disease (most deaths due to this) chronic obstructive lung diseases, including emphysema risk increases for those who start young, smoke many cigarettes and continue to smoke for a long time smoking is the single greatest avoidable cause of death.

LSD Pharmacology

odorless, colorless, tasteless and one of the most potent psychochemicals known - no known human OD--> LD50 is about 400x the behaviourally efective dose - absorbed rapidly through the GI tract - LSD is usually taken orally-- small dose has powerful effects. liquid solution may be taken orally. often applied to blotted paper and divided into squares containing single doses. - Half life is about 3 hours - metabolized by the liver and excreted as the inactive chemical *2-oxy-lysergic acid diethylamide* - tolerance develops rapidly within 3-4 days of daily doses. Recover from tolerance is also rapid. Cross-tolerance occurs among LSD, mescaline and psilocybin - physical dependence to LSD or other hallucinogens has not been shown - sympathomimetic agent--> autonomic signs appear quickly following administration: dilated pupils, elevated temp and BP, increased salivation - LSD mlcl resembles serotonin. Best evidence indicates that LSD acts by stimulating the serotonin-2A subtype of receptor

Oboliuqui (Morning Glories)

seeds of the morning glory plant Rivea corymbosa used as psychoactive agents in Mexico in the 16th century. Has religious significance - contains several active alkaloids, including d-lysergic acid amide.