Illicit Drugs GHB. How GHB is Used. GHB Recreational Use. GHB Effects (1) Oral intake. GHB:Gammahydroxybutyrate or Sodium Oxybate

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1 GHB:Gammahydroxybutyrate or Sodium Oxybate Illicit Drugs Wendy Porteous 2014 Fantasy, grievous bodily harm (GBH), liquid ecstasy Laboratory manufactured. Also produced in the brain through synthesis of GABA Developed as an anaesthetic, but withdrawn Sedative effects vary between individuals Affects some neurotransmitters. GHB Recreational Use Like alcohol, used as a recreational intoxicant Associated with dance music scene May assist with sleep Body builders may use GHB to increase production of growth hormone. How GHB is Used Form colourless, odourless liquid (from powder mixed with water). May be slightly salty or bitter to taste. Dose usual dose is around 1 3 g powder; approx. 1 g : 1 ml water (i.e. 5 g per teaspoon). Concentration is widely variable. Route oral, less often IV. Onset minutes. GHB Effects (1) Small dose (1 3 g) Decreased inhibitions Increased libido Euphoria similar to ecstasy Sedative effects Memory loss (sedation) Synergistic effect when combined with alcohol (significantly increases risk of overdose). Larger Dose (4 5 g) Powerful sedative effects Nausea and vomiting Stiffening of muscles Disorientation Profound sedation Convulsions Coma Respiratory collapse. Oral intake GHB Rapidly absorbed Maximal plasma concentration in minutes, dose dependent Clinical effects evident in 5-15 minutes Half-life = 30 minutes, dose dependent Eliminated via expired CO 2 1

2 Neurologic GHB Inhibits noradrenaline release Low doses inhibit dopamine release High doses mediate dopamine release Produces increase in growth hormone Mediates release of endorphins GHB Neurologic continued Naturally found in the CNS Toxicity hallmark is CNS depression short term amnesia and hypotonia respiratory depression and agitation drowsiness and sleep profound hypnosis and coma Cardiovascular GHB Bradycardia, decreased SVR and hypotension Studies have shown tissue protective effects from reducing oxygen requirements and unknown mechanisms GHB - Emergency Management Severe agitation reassuring environment electrolytes Coma airway protection O 2 therapy and ventilatory support IV therapy Methamphetamine - Ice Methamphetamine Amphetamine derivative Also known as Speed Meth Crystal Crank Tina Ice (4-methyl-aminorex) 2

3 Methamphetamine Can be taken orally, snorted, smoked or injected Onset immediate with IV, oral Duration ~4-8 hrs, Half life 4-6 hrs Drug testing Urine up to 1-3 days Blood up to 1-3 days Hair up to 90 days Dose Depends on frequency of use and tolerance. In pure form ~50 milligrams can be fatal for a non-user Effects Similar to cocaine Euphoria Hyperexcitability, Extreme nervousness Tachycardia, Vasoconstriction Sweating, dizziness Restlessness, insomnia Tooth grinding, incessant talking Bronchodilation Pupil dilation Some evidence can improve mental capacity Effects Severe hyponatraemia and cerebral oedema have been reported Mechanism thought to be due to psychogenic polydipsia and IADH Some studies have shown permanent destruction of serotonergic and dopaminergic neurons Treatment No specific antidotes Treatment is largely symptomatic Treat and support body systems ABCDE Oxygenation and ventilation Cooling for malignant hyperthermia Sedation for hyperactivity Chlorpromazine to block serotonin syndrome Beta blockers Fluid resuscitation Correction of electrolytes and acid base disturbance Surgery for haemorrhage Chemical name Ecstasy 3,4 methylenedioxymethamphetamine (MDMA) related to amphetamines Other names E, XTC, Eccy Adam, Eve, love drug, party drug MDMA/Ecstasy: 3,4-methylenedioxymethamphetamine MDMA is generally classed as a stimulant with mild hallucinogenic properties MDMA enhances extracellular concentrations of: serotonin dopamine All amphetamine-type substances share common effects and problems related to their use. 3

4 How Ecstasy is Used Forms tablets, capsules, powder, liquid Routes of administration oral (crushed / snorted), smoked, anal ( shelved ) or inserted in vagina ( shafted ), some IV use Dose normally mg in one good quality tablet usual dose is 1 2 tablets, although more may be taken if desired effect not reached. The Ecstasy Experience Coming up Tightening of muscles, esp. jaw dilated pupils, visual distortions Smooth or sudden nausea or vomiting Strong pulse, incr. temp Confusion, panic. 0 Plateau Feel good, happy, relaxed, open, loving Heightened senses Energy, confident, talkative Decreased urine output Increased thirst. Coming down Physical exhaustion, flat, depressed, tired, anxious irritable, paranoid Comedown more intense if IDU / polydrug user 4 8 Hours After Ingestion Pharmacokinetics Oral intake Initial effects usually minutes Initial rush is followed by plateau phase with peak effects at 90 minutes and may persist for 4-8 hours May take multiple doses stacking Action duration 8-24 hours with a half life of hours Metabolised by liver with renal excretion Pathophysiology Common effects empathy, euphoria lack of inhibition, increased sensuality, erectional dysfunction deep insight, panic attacks Rare effects: auditory & visual hallucinations As the high wanes feelings of depression, fatigue & irritability known as Tuesday Blues Pathophysiology Cardiovascular Autonomic hyperactivity with catecholamine surges Tachycardia and hypertension Heart failure and fatal arrhythmias more likely with pre-existing disease (pulmonary and cardiac, eg WPW) Hyperthermia Pathophysiology Neurologic Dilated pupils causing blurred vision Short-term hypertensive surges Subarachnoid and intracranial haemorrhage Cerebral infarction Vessel disruption more likely with preexisting disease Bruxism (teeth grinding) & trismus (jaw grinding) is common 4

5 Pathophysiology Serotonin syndrome Altered conscious state Muscle cramping or rigidity Increased BMR Hyperthermia (can be up to 42.8 o C) & dehydration Vigorous dancing at high temperatures can lead to muscle breakdown - rhabdomyolysis Pathophysiology Hyponatraemia Increased serum osmolality causes antidiuretic hormone (ADH) release ADH secretion fails to turn off Syndrome of inappropriate ADH release (SIADH) results Increased water intake can lead to water intoxication However, some have blunted thirst sensation Seizure and death Emergency Management Supportive management as no specific antidote Acute panic reassuring environment oral benzodiazepine Severe agitation electrolyte management Seizure DRABCD IV diazepam or clonazepam Emergency Management Aggressive cooling for malignant hyperthermia Sedation for hyperactivity Chlorpromazine to block serotonin syndrome Avoid beta blockers with tachycardia as potential for unopposed alpha effects Dantrolene for hyperthermia Synthetic Cannabis (Herbal Cannabis) Synthetic Cannabinoids The chemical structure of synthetic cannabinoids is different to THC (the active component of cannabis) however they both act on the cannabinoid system in the brain producing similar effects. Synthetic cannabinoids are usually sold combined with herbs and aim to mimic the effects of cannabis. Usually consist of dried herbs that are sprayed with synthetic cannabis. Then smoked for their cannabis like effects 5

6 Synthetic Cannabis Found in products with brand names such as: Kronic Northern Lights Kaos Spice Mango Voodoo Intense Incense K2 Tai Fun (Blackberry, Vanilla, Orange) Exclusive (Original, Mint, Cherry) Chill Zone (Berry, Mint, Original) Chill Out (Cherry, Mint, Original) Sensation (Vanilla, Orange, Bkberry) Chaos (Mint, Original, Cherry) Zen Zen Ultra WHAT S IN THESE INCENSE PRODUCTS? Listed Ingredients in Spice Canavalia rosea: beach bean or bay bean Nymphaea caerulea: Blue Egyptian water lily Scutellaria nana: Dwarf skullcap Pedicularis densiflora: Indian warrior Leonotis leonurus: Lion's Tail and Wild Dagga Cannabis like effect Zornia latifolia: is a perennial herb Nelumbo nucifera: Lotus Leonurus sibiricus: Honeyweed or Siberian motherwort Vanilla Honey Preparation of the incense : Botanicals (vegetable matter) are sprayed with liquid preparations of: HU-210 HU-211 CP 47,497 JWH-018 JWH-073 Origins of Synthetic Cannabinoids CP 47,497 - developed by Pfizer in 1980 as an analgesic HU-210 & HU synthesized at Hebrew University, Israel in HU-210 is an antiinflammatory; HU-211 as an anaesthetic JWH-018 & JWH synthesise by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffman more than 100 different synthetic cannabinoids have been created Usage Mode of use: Smoked Drink as an infusion/herbal tea 6

7 Availability Sold in metal-foil sachets Typically contain 3 g of smoking mixture sufficient for 8 joints Typical cost is dollars per pack Often sold as incense labelled with disclaimer: not for human consumption Smoking Cannabinoids What does CB 1 receptor control? Basal Ganglia: motor control, learning Hippocampus: memory, spatial navigation Cerebrum: cognitive functions - attention, language, emotions *CB2 found in blood cells, immune tissue and spleen.? in CNS Pharmacological Effects of Synthetic Cannabinoids are Similar to THC Dual effects: Herbs (very little medical literature of effects) Synthetic cannabinoid Mental (these affects predominate): Altered state of consciousness Mild euphoria and relaxation Perceptual alterations (time distortion) Intensification of sensory experiences Pronounced cognitive effects Impaired short-term memory Anxiety Paranoia Avoidant eye contact Agitation Delusions (paranoid, grandiose) Psychosis Pharmacological Effects of Synthetic Cannabinoids are Similar to THC Physical: Increase heart rate & blood pressure Dry eyes Diaphoresis Mild decrease in potassium Seizures Reduction in motor skill acuity Increase in reaction times Dependence Syndrome Similar to Marijuana Withdrawal: Inner unrest Drug craving Nightmares Profuse sweating Nausea Tremor Headache Hypertension Increased HR 7

8 Reported Effects of Synthetic Cannabinoids are Different Than THC Production inconsistencies Herbal incense blends are harsher to inhale Effect on appetite is non-existent Increased restlessness & aggressive behaviour Herbal incense produces a shorter high (perceptual alterations & sensory effects are limited) Doesn t mix well with alcohol (hangovers) Incense costs more than marijuana Spice Adverse Effects Used for its psychoactive and hallucinogenic effect Some reports of relaxation and sedation, but less euphoria than cannabis Report of rapid tolerance leading to increased dose Withdrawal, including internal unrest, tremor, palpitation, insomnia, headache, diarrhoea, nausea, vomiting Report of imperative voices (being told to act a certain way) as well as recurrent paranoid hallucinations Report of tachycardia and loss of consciousness No oversight of manufacturing process Could have multiple chemicals with unknown potency mixed with herbs 5-200x more potent than THC in marijuana Psychotic symptoms Toxicology Letters 197 (2010) Navy Times News, 06 June 2011, Psych Resident: Spice s Effects could be Serious, Long-Lasting Management No pharmacologically specific antidote Supportive care Benzodiazepines for agitation and anxiety Intubation in one case for decreased respiratory rate Duration of effects??? Illicit Drug Analogues and Derivatives Cathinones Synthetic derivatives of cathinone, a naturally occurring stimulant found in the khat plant (Catha edulis) of eastern Africa and the Arabian Peninsula. Although many cathinones have been synthesised for recreational use, mephedrone and 3,4-methylenedioxypyrovalerone (MDPV) account for most reports of toxicity. The most common routes of administration are nasal insufflation and oral ingestion. These drugs are commonly sold as white- or tancoloured crystalline powders that are labelled as bath salts and/or marked as not for human consumption to avoid detection Cathinones Because synthetic cathinones are structurally and pharmacologically similar to amphetamines, adverse effects associated with these compounds resemble those of other sympathomimetics. The most common features of sympathomimetic toxicity seen among users of synthetic cathinones presenting to emergency departments were agitation (38.9%), palpitations (25.0%), hypertension (13.9%) and tachycardia (36.1%). Life - threatening hyponatraemia and hyperthermia are uncommon but have been associated with death. Because basic drug screens do not detect synthetic cathinones, a high index of suspicion for these compounds is required when evaluating patients showing signs of a sympathomimetic toxidrome 8

9 4-MMC Mephedrone, 4-methylmethcathinone Present in products marketed as plant food and bath salts not for human consumption 4-Methylmethcathinone is a synthetic stimulant with euphoric and empathogenic effects that gained popularity in the U.K Thought to have similar actions to amphetamines Terminology / Slang Mephedrone, 4-MMC, Meow, M-Cat, Plant Food 4-MMC Usually taken as capsules or powder Effects last 2-3 hours when taken orally Negative effects appear to be dose related and are similar to ecstacy/mdma and include: Desire to redose, uncomfortable changes in body temperature (sweating and chills) Palpitations, impaired short term memory, insomnia Tightened jaw muscles, grinding teeth, and light headedness Mephedrone Adverse Effects Intense alertness, euphoria Empathy, talkativeness Intense sensory input Sexual arousal Perceptual distortions Hallucinations Severe paranoia Aggression Panic attacks Headache, tremors, blurred vision, seizures Anxiety, agitation, aggression, depression, psychosis Tachycardia, elevated BP, chest pain Body temperature lability Nausea, vomiting, diarrhoea Renal dysfunction, urinary retention BATH SALTS Psychopharmacology, DOI: /s x. Published online 12 Nov U.S. DOJ DEA. Office of Diversion Control. Accessed at Bath Salts: Ivory Wave Ivory Pure Ivory Coast Purple Wave Vanilla Sky What s in Bath Salts Cathinone Known for centuries Active metabolite is cathine Found in leaves and twigs of Khat plant (Catha edulis) Original synthetic cathinone is methcathinone 9

10 Mephedrone Reformulation of cathinone is a chemical found in the khat plant of Eastern Africa Khat existence traced to 15th C. Ethiopia Grown in Somalia, Yemen, Kenya, Ethiopia Bath Salts Bath salts contain the active ingredients methylenedioxypyrovalerone (MDPV) and mephedrone. MDPV is a synthetic psychoactive drug with stimulant properties that have been likened to ecstasy. Mephedrone is a synthetic stimulant with amphetamine-like or cocaine-like effects. These molecules are very similar to amphetamines, cocaine and other stimulants. Bath Salts Known to be in use in Australia since early 2010 Ordered as Ivory Wave through research chemical websites in Europe Arrests in Qld, NT and known to be in Victoria since early November 2011 Also known as Fake Cocaine Bath Salts Sold in 500mg packets labelled for novelty use only, a soothing bath salt. Contains a mix of several substances including the chemical methylenedioxypyrovalerance (MDPV) Bath Salts Similar properties and effects to MDMA (ecstacy) Usually snorted, smoked or injected Administration white/brown powder; capsules and tablets also available Oral (mouth, bombing ) Intranasal (snorting, keying ) Intramuscular Intravenous Rectal Gingival Inhalation via smoking 10

11 Onset and Duration of Action Onset: Mephedrone min Methylone min MDPV min Duration Mephedrone 2 5 hrs Methylone 2 5 hrs MDPV 2 7 hrs 1. Inhibitor of reuptake of dopamine, serotonin and noradrenaline 2. Increased presynaptic release of same monoamines though less effect than number 1 Pharmacological Effects of Bath Salts : Physical: Increase heart rate & blood pressure Pupil dilation Dizziness Nausea Breathing difficulties Headache Chest pain Bruxism Tremors Insomnia Myocardial infarction Pharmacological Effects of Bath Salts : Mental: Hyperactivity, arousal & over stimulation Increased energy & motivation Euphoria - agitation Diminished perception of the requirement for food and sleep Talkativeness Increases sexual arousal Crave to redose frequently Health Hazard? Bizarre behaviour Phenomenal physical strength Self mutilation Suicide Persistent paranoid psychosis Persistent symptoms of paraesthesias and mood changes for days to weeks after using Dependence Like amphetamines induce tolerance and dependency in at least 30 percent of users with craving and impaired control 11

12 Long Term Effects Little is know as relatively recent use Potential neurotoxicity with decrease dopamine transporter activity in the basal ganglia leading to a parkinson s like disorder No specific antidote exists Supportive care Aggressive sedation with benzodiazepines for increased heart rate, seizures, agitation and hypertension Avoid beta blockade due to potential exacerbation of hypertension due to unopposed alpha-adrenergic stimulation Hyperthermia may require cooling If severe (persistent vital sign elevation, neuro and psychiatric abnormalities), all patients should be admitted and have: ECG Serial temperature checks CK Electrolytes Renal/liver functions Management NBOMe Cathinone 2C agents Known as synthetic LSD Severe psychedelic effects Usually sold as blotters Usually taken sublingually or intranasally Street names N-bomb, Smiles,25I, 25C, 25B, Spice, Melting, Smiley Paper, Phenethylamines Agonist/antagonist 5-HT receptor Hallucinations Over-stimulation & agitation (amphetamines) Multiple forms Tablets, capsules, powder for insufflation Kinetics Onset 20 min, peak 2 hrs, duration 6-12 hrs Phenethylamines Clinical Effects Hallucinations, agitation, seizures Hyperthermia, tachycardia, hypertension, tachypnoea Extreme/rapid cycling emotions Mydriasis, flushing, diaphoresis Nausea, vomiting, Facial dystonia (teeth grinding, grimacing) Rhabdomyolysis Phenethylamines (cont) Insufflation - immediate pain nasal mucosa 12

13 References Australian Drug Trends 2008: Findings from the Illicit Drug Reporting System (IDRS). NDARC Monograph Sydney, National Drug and Alcohol Research Centre. University of New South Wales. Erickson, T., Thompson,T., & Lu, J. (2007), The approach to the patient with an unknown overdose. Emergency Medicine Clinics of North America 25: Holstege, C., Dobmeier, S., & Bechtel, L. (2008). Critical care toxicology. Emergency Medicine Clinics of North America 25: Regan,L., Mitchelson,M.& Macdonald, C. (2011) Mephedrone toxicity in a Scottish emergency department. Emerg Med J 28:1055e1058. doi: /emj Durham, D. (2011) Ivory wave: the next mephedrone? Emerg Med J 28:1059e1060. doi: /emj McGraw, M. (2012) Is your patient high on bath salts? Nursing (1) DOI /01.NURSE d0 North, J. (2011) Mitigating the risks of methamphetamine. Emergency Nurse 19(6) Devlin, R. & Henry, J. (2008) Clinical Review: Major consequences of illicit drug consumption. Critical Care 12:202 (doi: /cc6166) Watson, C. & Wilkinson, J. (2010) The intensive care management of common and uncommon drugs of misuse. British Journal of Hospital Medicine 72(4)