Legal highs cardiff lecture

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  • 1. Herbal Highs: Effects and Consequences Andrea Zangara Flordis Natural Medicines Medicinal Plant Research Centre (Newcastle University, UK) Brain Science Institute (Swinburne University, AU) andrea@flordis.com Embracing Diversity, Drugs and Differences 15th October 09 Marriott Hotel, Cardiff
  • 2. Classification of Psychoactive Drugs: drugs which alter mood states and consciousness drugs used in the treatment of psychopathology stimulants hallucinogens depressants anxiolytics anti-depressants antipsychotics
  • 3. Cocaine: background • isolated from coca plant (Erythroxylon coca) • historical use in Colombia and Bolivia (largely to aid strenuous manual work)
  • 4. Cocaine: history • cocaine itself isolated in mid nineteenth century • historical use in various beverages and tonics advertisement 1885
  • 5. Vin Mariani introduced 1863
  • 6. Cocaine: properties • 0.6 - 1.8% in coca leaves • usually administered as powder (cocaine hydrochloride) or crystalline rocks
  • 7. Administration • oral ingestion –slow rate of absorption –relatively steady state • onset from other routes –snorting - 3 mins –injection - 15 secs –smoking - 5 secs ‘rush’ ‘crash’
  • 8. Acute behavioural effects • increased confidence, exhilaration and alertness • decreased fatigue and boredom • delays onset of REM sleep • facilitates sustained effort • enhances athletic performance
  • 9. Cocaine risks and damages • psychological addiction, compulsion • breathing troubles, risk of stroke, heart attack, seizures • insomnia, weight loss, depression, irritability, exhaustion, incoherence, delusions aggression • toxic psychosis (similar to paranoid psychosis) • symptoms caused by ‘crack’ may be more persistent • large doses can directly damage neurons • physical damage
  • 10. Cocaine mix • Alcohol: cocaethylene extends effects and increases cardiovascular toxicity • Amphetamines: rare, similar effects; increase toxicity and cardiac stress • Cannabis: smoked to relax (might increase blood pressure and heart rate) • Ecstasy: popular mix as ‘dance drug’; increases physical and mental stress • Heroine: ‘speedball’, the 2 drugs amplify each other and the heart can ‘lose rhythm’ • Ketamine: popular mix for dancing • Viagra: can be dangerous (cardiovascular)
  • 11. Amphetamine: background • 1924 ephedrine isolated from Chinese ma huang (Ephedra vulgaris) • replaced by synthesised amphetamine in 1927 – rediscovered from 1887 as ephedrine substitute • chemical structure related to adrenaline and noradrenalin • widely used in military scenarios (to this day) • popular recreational drug in certain subcultures
  • 12. Amphetamines • Speed (amphetamine sulphate) • Base • Methamphetamine • Ritalin
  • 13. Amphetamines: effects • snorted, injected, smoked, ingested • administration influences onset • effects similar to cocaine but longer • CNS continually stimulated • suppression of appetite, sleep, increased concentration, confidence • grinding teeth • ‘crash’, in 3-8 hours
  • 14. Amphetamines: risks and consequences • risk of overdose (injection) • chronic use: paranoia, tension, depression, fatigue, total exhaustion • chronic use and large acute intake can trigger amphetamine psychosis (paranoia, obsessions) • highly addictive • tolerance is rapid • withdrawal = opposite symptoms
  • 15. Amphetamines mix • Additional strain on the heart and increased blood pressure • Alcohol: very popular, can drink more • Cannabis: to relax • Cocaine: similar effects, increase cardiovascular risk • MDMA: extend and intensify; body temperature up • Heroine: popular mix, decreases paranoia • Ketamine: perception changes (time) • Magic mushrooms: more paranoia • Tobacco: more cigarettes
  • 16. LSD (acids, trips) • Lysergic Acid Diethylamide • Synthetic, with profound effects on perception and cognition at very low doses (40-150 mcg) • LSD has main effects on 5-HT (serotonin) neurons • Colourless, odourless, tasteless: generally LSD is typically delivered orally, usually on a substrate such as absorbent blotted paper, sugar, or gelatine • Difficult to understand quality and quantity as it rapidly degrades
  • 17. Effects • effects appear from 20 mins to 2 hours • initially euphoria, goose bumps, increase in heart rate, jaw clenching, perspiration, pupil dilation, hypothermia, nausea • between 30-45 minutes to reach their peak • profound modification of consciousness, synaesthesia • 8-12 ore in total • after effect: tiredness, positive or negative feelings • set e del setting very important
  • 18. LSD: risks and consequences • bad trips • excessive dose • irresponsible actions • flashbacks • insomnia • extreme paranoia • personality disintegration / psychosis
  • 19. MDMA (Ecstasy) (3,4-methylenedioxymethamphetamine) • Related to both amphetamines and hallucinogenic (DA e 5HT) • Empathogens as first ‘designer drugs’ • MDMA, MDA, MDE, 2CB, 2CT, 4-MTA, DOB.... • In pills and powder form (md) • Effects starts after 20-40 mins, and last 4-5 hours • Physiological effects similar to amphetamine • Positive feelings of elation, euphoria, and closeness to others, appreciation of music and touch; replaced by depression and lethargy in the days afterwards • Regular use may be neurotoxic, with prolonged serotonergic damage
  • 20. Self-reported memory deficits in recreational drug users: findings from web-based studies Andrew Scholey, Jacqui Rodgers, Tom Buchanan, Tom Heffernan, Jonathan Ling and Andy Parrott 1Human Cognitive Neuroscience Unit, University of Northumbria 2Doctorate in Clinical Psychology, University of Newcastle 3Department of Psychology, University of Westminster 4Psychology Department, Keele University 5Department of Psychology, University of Swansea Human Cognitive Neuroscience Unit www.hcnu.com Sydney ICOM July 2006
  • 21. Summary • self-report data are consistent with laboratory studies of memory deficits and other impairment • internet provides insights into perceived problems and motivations • future studies should include – online cognitive testing – use of PRMQ – relationship between subjective and objective measures – prospective longitudinal studies starting in schools?
  • 22. Gender effects • Recent reports have suggested that women are more susceptible than men to acute and sub-acute effects of ecstasy • We found no gender differences – chronic effects equivalent in males and females? – chronic effects lead to poorer calibration? males females REPORTEDERRORS 0 1 2 3 males females ERRORS 0.0 0.5 1.0 PMQ-LT ERRORS COMPLETING FORM Rodgers et al (2003) J Psychopharmacology 17, 379-386
  • 23. Heat, ecstasy and LT-PM • animal literature indicates contribution of hyperthermia to MDMA serotonergic toxicity • here individuals who stated that they danced and became hot while on ecstasy reported more PM-LT difficulties Parrott et al (2006) Hum Psychopharmacology In press
  • 24. Chronic physiological effects of MDMA • Demonstrated to cause serious 5-HT neurodegeneration • In humans regions of destruction – Hippocampus – Frontal cortex
  • 25. Ketamine • Dissociative anaesthetic : sense of detachment from one's physical body • Appearance: powder, tablets, liquid • Effects last 45-60 minutes: from mild stimulation to out-of-body and near-death experiences • Ketamine blocks glutamate activity, the result is a temporary shut down of some brain areas (K-hole)
  • 26. Ketamine: risks and consequences • ketamine can be extremely habit forming • relatively safe • dangerous in combination with other depressants • danger of physical harm • chronic use: troubles in digesting properly, urinating, memory weakening, alienated and dissociated states • tolerance develops quickly, but no withdrawal (restlessness)
  • 27. The use of psychoactive plants Humans have a natural drive to pursue ecstatic experiences All cultures have developed methods for inducing such experiences Every culture in the world (has) used psychoactive plants
  • 28. Cannabis • The most used drug (illegal) • Hashish 10-20% THC • Marijuana 5-15% • Smoked • Ingested
  • 29. • Over sixty active cannabinoids identified • most prominent intoxicant - D9-tetrahydrocannabinol (D9-THC) – also e.g. D8-THC (relatively little) • up to 20% of dry weight leaf • also cannabinol (CBN) and cannabidiol (CBD) – not themselves active – may alter potency of active ingredients • burning also modifies CBD into THC • content is variable and changing historically • Modern strains contains up to 3 times THC Active ingredients
  • 30. Cannabis and psychosis • International Cannabis and Mental Health Conference (2007): CBD as anti psychotic; THC seems to interact with brain areas related to paranoia and anxiety • amisulpride and CBD in 42 psychotic patients: improvement of symptoms and less side effects with CBD (Leweke, 2007) • CBD modulates THC? • New strains unbalanced?
  • 31. Legal / Herbal Highs • Legal mind-altering substances, which cause similar effects to illegal drugs • Processed and unprocessed psychoactive herbal/vegetable products (mushrooms, plants, cacti, seeds, roots etc…) • Synthetic products • Various mixes and extracts (5x…) • Categories: – Energy (stimulants) – Relaxant – Aphrodisiacs – Psychedelics – Detox/ Prepare/ Repair
  • 32. Contexts and Typologies Contexts • Prohibition • Harm reduction • Globalisation • New musical trends • Other contexts without music Typologies • Sensation seeker (psychonauts) • Experimental drug users attracted by media • Those wanting a legal alternative to illegal drugs • Poli drug users •Curious
  • 33. Smart Drugs and Smart Shops • Eighties: nootropics • Nineties: detox, prepare and repair, herbal ecstasy, ‘herbal highs’ • Smart shops: from Netherlands to EU • Today: synthetic legal highs, increasing strength, Internet
  • 34. Number of the total identified online shops by country selling legal alternatives to illegal drugs Country Number of sites Austria 3 Ireland 1 Portugal 1 Germany 4 Netherlands 25 UK 35 Total 69 7 out of 27 selected for further analysis offered more than one language version A total of 8 different European languages were covered by the 27 online shops Source: European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) 2008
  • 35. How Safe? • NZ: Survey of patients and relatives presenting to an emergency department (n=1043) • 11.9% had taken herbal party pills (30% among 14-25 year olds) • 84.8% had felt effects from party pills • 50.4% described effects as “good” • 4.8% had sought medical attention for effects Source: Nicholson, T.C. (2006), Prevalence of use, epidemiology and Toxicity of “herbal party pills” among those presenting to the emergency Department.
  • 36. 60 times than nature!
  • 37. Herbal Highs: Policies • ‘Herbal highs’ — pose a range of difficult questions for drug control policies: • Conceptual: how to define which products are of interest • Practical and methodological: how to monitor the products sold, identify the synthetic compounds that they may contain and assess their health risks • Little knowledge about the pharmacology, toxicology and safety profile in humans, the type and amount of synthetic substances added may vary considerably
  • 38. The Smart Alternative (harm reduction) • Herbal XTC → MDMA/Stimulants • Magic mushrooms → LSD • GHB → Opiates The ban on them had as consequence: BZP – Amanita muscaria – Synthetic cannabinoids – Research chemicals
  • 39. Herbal ecstasy (ephedra/ ma huang/ sida cordifolia /sinephrine) • Sympathomimetic amine acting on adrenergic receptor system • Similar in structure and effects to the synthetic derivatives amphetamine and methamphetamine • Euphoria, stimulant, appetite suppressant, bronchodilator, thermogenesis • Can cause insomnia, nervousness, heart-problems and high blood pressure, stroke, and seizures • Cardiovascular risk increases when combined with other stimulants • Can increase tolerance to alcohol effects
  • 40. Synthetic Stimulants/ Legal Highs
  • 41. Not so smart ingredients (little or unknown long term risks) • Butylone • Methylone • Methedrone • Mephedrone • Methcathinone • Dimethylcathinone • Synthetic cannabinoids • Piperazine • Benzylpiperazine • 3-Trifluoromethylphenylpiperazine
  • 42. Benzylpiperazine (BZP) • Piperazines, not herbal but sold due to amphetamine-like effects and legal • Benzylpiperazine (BZP) is the most common derivative • Piperazine was originally used as an antihelmintic to treat round worm • Derivatives were further investigated in the 1970’s but trials stopped when abuse potential was clear
  • 43. Benzylpiperazine (BZP) The effects • Loss of appetite, increased heart rate, tingling skin and flushing ,sense of euphoria and increased alertness; • Sense of taste, sound and colour may be enhanced; • Such effects can last between four to eight hours, depending on the amount taken, the user's mood, metabolism and environment. The risks • Users report an inability to sleep for as long as 10 hours after the effects have subsided • Can leave users with symptoms similar to a hangover, such as headache, fatigue, reduced appetite and nausea • Possibility of slight memory loss • BZP has been linked to cases of seizure, renal failure and acute psychosis in some studies. Mixing BZP with other drugs, including alcohol, may increase risk of negative effects. • The law: • At present, a loophole in the UK law allows BZP to be sold as a soil fertiliser.
  • 44. Containing 180mg of BZP and TFMP. Plus lots of other nutrients and minerals • The combination of BZP and TFMPP has been associated with a range of side effects (insomnia, anxiety, nausea and vomiting, headaches and muscle aches similar to migraine, seizures, impotence, rarely psychosis), as well as a prolonged and unpleasant hangover effect similar to that produced by alcohol. These side effects tend to be significantly worsened when the BZP/TFMPP mix is consumed alongside alcohol (Wilkins C. Et al., 2007)
  • 45. Doves • LONDON UNDERGROUND INVITES YOU TO GROW WITH LOVE!! Get ready for London Undergrounds latest addition to our NON BZP range. Doves are the crème de la crème of London Undergrounds pills and its best kept secret. • Now available BZP & TFMPP free. Doves Feeder encourages healthy leaf growth and strong root development. Doves Feeder is suitable for use on indoor and outdoor plants. DOVES are available to customers outside USA, Australia and New Zealand. Doves are available in 2 packs and 5 packs. • Recommended dosages DIRECTIONS: Use one Dove feeder per square meter around garden beds. For potted plants use half a Dove feeder toward outer edge of the pot. Use half this amount for Violets and ferns. ALWAYS WATER IN WELL AFTER APLICATION. • Do not contain methylone/ethylone NOT FOR HUMAN CONSUMPTION SOLD AS PLANT FOOD The Dove pills are a state of the art product. They don't contain the DOMS but a beta ketone. Structurally this ketone is very similar to MDMA, but while that is controlled under the Misuse of Drugs Act 1971 the ketone isn't. Nor does it fall into any of the Analogue Laws or sub clauses of the Misuse Act. It is not a phenethylamine •
  • 46. Magic Mushrooms • Active ingredients: psilocybin and psilocin (varies) • Both mimic serotonin action - so effects may be through serotonin receptors. • Over 90 species of magic mushrooms worldwide • Similar effect to LSD, but shorter, less intense • Eaten (fresh or dry) or drank as tea • Dose: 2 gr (dry), 20 gr (fresh) • Modification of perception dose-dependent • Effects after 20 mins, peak at 30-45 for 1-2 hours, total 4-6 hours
  • 47. Risks and consequences • Exaggerate negative feelings • Wrong setting • ‘Bad trip’: fear, nausea, anxiety, confusion, fainting • Memory impairment • Latent or pre existent psychosis • Poisonous mushrooms • High turnover UK Treasury sales tax on hallucinogenic mushrooms: 255,000 Euro per year on a turnover of approx. 1.46 million Euro per annum (estimations)
  • 48. Fly Agaric (Amanita muscaria) • Ibotenic acid converted to muscimol on drying or in the body; same effects, but muscimol is 5-10 times more potent
  • 49. Effects • Psilocybe and Amanita are not chemically related with regard to their psychoactive properties: markedly different psychoactive effects • Effects can be felt 30-120 minutes after ingestion. The peak will start 1-3 hours after ingestion and can last 6-10 hours. After effects can last another 1-6 hours. Alcohol can intensify intoxication • Marijuana can ease any feelings of nausea and intensify intoxication.
  • 50. Effects cont. • Low dose = 1-5 grams dried (1-2 fresh mushrooms) medium dose = 5-10 grams dried (2-4 fresh mushrooms) high dose = 10-30 grams dried (4-10 fresh mushrooms) • Visual distortions, mood changes, euphoria, relaxation, delirium, inebriation, spasms. • High doses give swollen features, high rage and madness, characterized by bouts of mania, followed by periods of quiet hallucination. • Fatal dose = 10 mushrooms (ca. 100 g fresh mushroom). • No antidotes! - stomach pumped
  • 51. Synthetic Cannabinoids (Spyce) • Herbal blend that claims to be a legal substitute for cannabis • Advertised as an ‘exotic incense blend which releases a rich aroma’ and ‘not for human consumption’ • Some of the declared ingredients are plants traditionally known as ‘marijuana substitutes’ • Most of the ingredients listed on the packaging are actually not present in the Spice products • It is assumed effects described by users are due to added synthetic cannabinoids Information fom Dr. R. Sedefov, Lisbon, 15 June 2009
  • 52. Synthetic Cannabinoids (Spyce) • In 2008 a new psychoactive substance JWH-018 a cannabinoid receptor (CB) agonist identified in Spice products in Austria • Chemical structure differs substantially from THC, but it produces similar effects and more potent • Several synthetic cannabinoids discovered afterwards across EU • No pharmaceutical product has emerged, no human studies carried out • Little is known about metabolism and toxicology. The health risk of the inhaled smoke is unknown
  • 53. Synthetic Cannabinoids (Spice) • In the case of JWH-018 it can be assumed that due to structural features there may be a certain carcinogenic potential? • Active in low doses; accidental overdosing with a risk of severe psychiatric complications because the type and amount of cannabinoid may vary considerably • In general, there may be a risk for the appearance of a full CB receptor agonists; leading to life threatening conditions if overdosed? • Seems that tolerance may develop fairly fast; arguably this might be associated with relatively high potential to cause dependence
  • 54. Salvia divinorum • The Salvia genus is part of the Lamiaceae family (more commonly called the Mint family). The Mint family contains over 200 genera and 3,500 species • Salvia has a long history of use by the by the Mazatec people of Oaxaca, Mexico for divination, entheogenic, and healing purposes • Dried leaves: smoked (bong), chewed; solid or liquid extracts (5x-100x) • The main active chemical in Salvia divinorum is called salvinorin A
  • 55. Salvia: Effects and Consequences • Salvinorin A is an extremely powerful consciousness altering compound • When the herb is consumed either by smoking the dried leaf or chewing the fresh leaves the effects are usually (but not always) pleasant • When the dose goes above 500 - 1000 mcg the effects can be excessive –always need a ‘sitter’ • Hallucinogenic – psychedelic effect, but short (3’5 min), powerful, immediate; not a ‘dance drug’ • May trigger latent psychological and mental problems • Illegal from 2005 in some EU
  • 56. Salvia: Effects and Consequences • Most harms resulting from the use of psychoactive drugs like salvia occur as a result of people injuring themselves when under the influence of the drug • There is some concern that salvia could trigger psychotic episodes particularly in young people and vulnerable individuals with latent mental health problems
  • 57. Hawaiian Baby Woodrose (Argyreia nervosa) • LSA, simile a LSD (also Ipomoea) • Medical use: bronchitis, cough, diabetes, syphilis, tuberculosis, and other maladies. Also as aphrodisiacs, tonics, cognitive enhancer • Dose: 3-8 seeds in little pieces • Effect similar to LSD but more narcotic • Nausea (remove coating) • Overdosing is rare • Trigger psychosis or psychotic states
  • 58. Kratom • Mitragyna speciosa is the botanical name of the plant • From South East Asia; Kratom has been used as medicine in Thailand since ancient times • The primary active chemicals in kratom are mitragynine • At lower doses, has physically stimulating effect. At larger doses it is more sedating, with a relaxed, euphoric cerebral sensation, with some pain relieving properties (similar to those of a mild opioid like codeine)
  • 59. Effects and Consequences • Can ease the discomfort of withdrawl from opium and opium based substances like heroin, morphine • There is a chance of becoming addicted (if only psychologically) to kratom if abused • When taken orally, the effects of kratom can be felt about 30-60 minutes after ingestion, and the peak lasts 2-3 hours. When smoked, the effects start quicker and last about 60-90 minutes • The only common negative comment about kratom is that it causes nausea at high doses
  • 60. Other natural psychedelics • Cacti: Peyote / San Pedro (mescaline) • Ayahuasca (dmt / armaline) • Yopo (dmt) • Iboga (ibogaine) • Generally not considered ‘trendy’ and used only by experienced people
  • 61. RESULTS Sample characteristics  The average age of the interviewees was 24±5 years, 65 (64.4%) of whom were males, 36 (35.6%) females. Female smartshop customers were significantly younger than males (22.6±3.6 vs. 24.9±4.7, p=0.014). The average age at first visit to a smartshop was 20±3.8.  80.2% of the interviewees had bought energy drinks from a smartshop, 76.2% magic mushrooms, 58.4% herbs, 49.5% herbal XTC, 47.5% smart nutrients, 33.7% nootropics, and 20.8% strong psychoactive herbs. The strongest the product, the more the customer tend to be older and informed on the effects and consequences
  • 62. Conclusions: a missed chance? • Psychedelic herbs when out of their context or in forms different from traditional use may produce dangerous and unwanted effects • Smartshops should be honest source of information and literature on the contents, effect and safety of legal highs, never instigate or push use of anything • The original concept was not to provide completely safe products, but safer than illegal drugs and identifiable, and to give enough information for the safest use • The smart concept should include health and safety monitoring, quality and purity of products, liaison with health and regulatory authorities • Today’s trend seems only to get easy and fast money, and trick the law with new and potentially dangerous synthetic molecules, representing a serious hazardr to public health • A new and effective legal framework is urgently needed
  • 63. Have conscious dreams and remember: You can fly also without drugs!