MIND ALTERING… SYNTHETIC (DESIGNER) AND NATURALLY OCCURING…DRUGS

Cardwell C. Nuckols, PhD [email protected] www.cnuckols.com PHARMACOLOGICAL CATEGORIES • STIMULANT DRUGS – “BATH SALTS” – KHAT (CATHINONE) • CANNABINOIDS – “SPICE” AND A WIDE VARIETY OF CANNABINOID RECEPTOR AGONISTS • DEPRESSANTS – GHB PHARMACOLOGICAL CATEGORIES • HALLUCINOGENS – 2C-E AND RELATED SYNTHETIC PSYCHEDELIC PHENETHYLAMINES • THE NEUROSOUP GUIDE (http://www.neurosoup.com/neurosoup_trip_guide. htm ) – MDMA • 3,4-methylenedioxymethamphetamine – SALVIA DIVINORUM NEUROSOUP TRIP GUIDE PHARMACOLOGICAL CATEGORIES • OPIOIDS – KRATOM (7-HYDROXYMITRAGYNINE) – KROKODIL (DESOMORPHINE) • INHALANTS – JENKEM “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS “BATH SALTS” AND RELATED STIMULANTS • INGREDIENTS – 3,4-METHYENEDIOXYPYROVALERONE (MDPV) • MPPP • MDPPP – 4-METHYLMETHCATHINONE (MEPHEDRONE OR 4- MMC) • PHARMACOLOGY – MDPV IS A POWERFUL STIMULANT THAT FUNCTIONS AS DOPAMINE-NOREPINEPHRINE REUPTAKE INHIBITORS (NDRI) “BATH SALTS” AND RELATED STIMULANTS • PHARMACOLOGY (CONTINUED) – 4-MMC IS CHEMICALLY SIMILAR TO AMPHETAMINE AND KHAT, MANUFACTURED IN CHINA AND COMES IN TABLETS OR POWDER THAT CAN BE SWALLOWED, SNORTED OR INJECTED – THEY HAVE STIMULATORY EFFECTS ON THE CENTRAL NERVOUS SYSTEM (CNS) AND CARDIOVASCULAR SYSTEM – MDPV AND 4-MMC PHYSICAL SYMPTOMS INCLUDE RAPID HEART RATE, INCREASED BLOOD PRESSURE, VASOCONSTRICTION AND SWEATING “BATH SALTS” AND RELATED STIMULANTS • PHARMACOLOGY (CONTINUED) – MDPV AND 4-MMC MENTAL SYMPTOMS INCLUDE EUPHORIA, INCREASED ALERTNESS, INCREASED WAKEFULNESS, ANXIETY, AGITATION, AND REDUCED DESIRE FOR FOOD AND SLEEP – MDPV IS REPORTEDLY FOUR TIMES AS STRONG A STIMULANT AS RITALIN AND IS SOMETIMES LABELED AS LEGAL COCAINE OR LEGAL AMPHETAMINE “BATH SALTS” AND RELATED STIMULANTS • TRADE NAMES-SOLD AS PLANT FOOD AND FOR AROMATHERAPY ALSO – MDPV • “RED DOVE”, “BLUE SILK”, “CLOUD NINE”, “ZOOM”, “BLOOM”, “VANILLA SKY”, “SCARFACE”, AND “STAR DUST” • ALSO SOLD AS INSECT REPELLANT AND PLANT FOOD WITH NAMES LIKE “BONSAI GROW” – 4-MMC • “MEPH”, “DRONE”, “MCAT” AND “MEOW, MEOW” • DURATION OF EFFECTS – MDPV IS ROUGHLY 3-4 HOURS WITH AFTER EFFECTS LASTING 6-8 HOURS KHAT

• NATIVE TO TROPICAL EAST AFRICA AND ARABIAN PENINSULA – PART OF SOCIAL CULTURE IN SOME AREAS • FRESH LEAVES/TOPS CHEWED OR CONSUMED AS TEA • STIMULANT AND EUPHORIANT • CATHINONE (SCHEDULE 1) • STRUCTURALLY SIMILAR TO AMPHETAMINE KHAT PHARMACOLOGY

• EUPHORIANT (DOPAMINE) • ANOREXIGENIC • STIMULANT – DILATED PUPILS – INCREASED HEART RATE – INCREASED BLOOD PRESSURE • HYPNAGOGIC (AUDITORY DREAM LIKE) HALLUCINATIONS (COMING DOWN) KHAT KHAT KHAT KHAT KHAT KHAT “SPICE” AND OTHER SYNTHETIC CANNABINOIDS • INGREDIENTS – A DIVERSE GROUP OF CANNABINOID RECEPTOR AGONISTS FALLING INTO SEVEN MAJOR STRUCTURAL GROUPS • NAPHTOYLINDOLES • NAPTHYLMETHYLINDOLES • NAPTHOYLPYRROLES • NAPTHYLMETHYLINDENES • PHENYLACETYLINDOLES • CYCLOHEXYLPHENOLS • CLASSICAL CANNABINOIDS (DIBENZOPYRAN) SYNTHETIC CANNABINOIDS

• CANNABINOID AGONISTS-RESEARCH CHEMICALS – JWH-015 – JWH-018 – JWH-073 – JWH-081 – JWH-133 – JWH-200 – JWH-250 – JWH-398 – CP 47,497 – CP 55,244 – HU210 – WIN 55,212-2 CANNABINOID EFFECTS

• Appetite, feeding behavior and body weight • Reward and motivation • Mood and anxiety • Pain • Memory

CANNABINOID MODULATORS • Work on CB-1 and CB-2 receptor sites • Rimonabant (Acomplia) – Blocks CB-1 receptors – Suppresses appetite – Favorable changes in blood fats, cholesterol and glucose tolerance – High drop out rate RIMONABANT

• Clinical Trials – Test subjects • No psychiatric history • No family history – High Drop-out rate – Psychiatric Side-Effects • Anxiety • Depression

BRAINWORK (May-June 2006) CANNABINOID MODULATORS • Anxiety and depression involve the endocannabinoid system – Rimonabant blocks receptors • May see increase in psychiatric symptoms – If boost endocannabinoid system get antianxiety and antidepressant effects SYNTHETIC CANNABINOIDS- COMMERCIAL Rimonabant (also known as SR141716; trade names Acomplia, Bethin, Monaslim, Remonabent, Riobant, Slimona, Rimoslim, Zimulti, and Riomont) is an anorectic antiobesity drug. It is an inverse agonist for the cannabinoid receptor CB1. Its main effect is reduction in appetite. Rimonabant blocks the psychoactive and some of the cardiovascular effects of Δ9-tetrahydrocannabinol (THC) in humans without affecting the pharmacokinetics. SYNTHETIC CANNABINOIDS- COMMERCIAL • Dronabinol (Marinol, Delta-9- tetrahydrocannabinol, delta-9-THC) is synthetic THC. It is used to treat nausea and vomiting caused by chemotherapy in people who have already taken other medications to treat this type of nausea and vomiting without good results. Dronabinol is also used to treat loss of appetite and weight loss in people who have acquired immunodeficiency syndrome (AIDS). Dronabinol is in a class of medications called cannabinoids. It works by affecting the area of the brain that controls nausea, vomiting, and appetite. SYNTHETIC CANNABINOIDS- COMMERCIAL Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It is a synthetic cannabinoid, which mimics the main ingredient of cannabis (THC). Chemically, nabilone is similar to the active ingredient found in naturally occurring Cannabis sativa L. In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the U.S. Food and Drug Administration (FDA) for treatment of chemotherapy-induced nausea and vomiting that has not responded to conventional antiemetics. Though it was approved by the FDA in 1985, the drug only began marketing in the United States in 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS. Although it doesn't have the official indication (except in Mexico), nabilone is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrated various benefits for condition such as fibromyalgia and multiple sclerosis. SYNTHETIC CANNABINOIDS- COMMERCIAL Sativex is an oromucosal (mouth) spray developed by the UK company GW Pharmaceuticals for multiple sclerosis patients, who can use it to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms. Sativex is also being prescribed to alleviate pain due to cancer and has been researched in various models of peripheral and central neuropathic pain. Sativex is distinct from all other pharmaceutically produced cannabinoids currently available because it is derived from botanical material, rather than a solely synthetic process. Sativex is a pharmaceutical product standardized in composition, formulation, and dose. Its principal active cannabinoid components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). The product is formulated as an oromucosal spray which is administered by spraying into the mouth. Each spray of Sativex delivers a fixed dose of 2.7mg THC and 2.5mg CBD. SYNTHETIC CANNABINOIDS (SPICE) SYNTHETIC CANNABINOIDS SYNTHETIC CANNABINOIDS SYNTHETIC CANNABINOIDS {K2 (JWH-018, JWH-073)} “SPICE” AND OTHER SYNTHETIC CANNABINOIDS • PHARMACOLOGY – CANNABINOID RECEPTOR AGONISTS MIMIC THE EFFECTS OF THC AND ANADAMIDE BY INTERACTING WITH THE CB1 RECEPTOR IN THE BRAIN – SOME OF THESE SYNTHETICS HAVE A HIGHER AFFINITY FOR THE RECEPTOR THAN CANNABIS THC AND MAY BE PARTICULARLY LONG ACTING – OFTEN LARGE AMOUNTS OF TOCOPHEROL (VITAMIN E) ADDED TO MASK ANALYSIS “SPICE” AND OTHER SYNTHETIC CANNABINOIDS • PHARMACOLOGY (CONTINUED) – SMOKING MIXTURES ARE USUALLY SOLD IN METAL-FOIL SACHETS TYPICALLY CONTAINING THREE GRAMS OF DRIED VEGETABLE MATTER TO WHICH ONE OR MORE OF THE CANNABINOIDS HAVE BEEN ADDED • TRADE NAMES – “SPICE GOLD”, “SPICE SILVER”, “YUCATAN FIRE”, “CHILL X”, “SENSE” AND MANY OTHERS GHB (CNS DEPRESSANT)

• γ-Hydroxybutyric acid (GHB), also known as 4- hydroxybutanoic acid • Naturally occurring substance found in the human Central nervous System (CNS) • General anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance (elevates Human Growth Hormone). It is also used as an intoxicant or as a “date rape drug”. Has a salty taste like baking soda GHB

• Georgia Home Boy", "Juice", “Grievous Bodily Harm”, "Liquid Ecstasy", "Mils", "G", "Liquid X", and "Liquid G", as well as "Fantasy" • Its effects have been described anecdotally as comparable with alcohol and ecstasy use, such as euphoria, disinhibition, enhanced sensuality and empathogenic states GHB GHB GHB TOXICITY

• LOW DOSE (.5-1.5 GRAMS) • EQUAL TO 1-3 ALCOHOLIC DRINKS) – Reduces anxiety – Acts as a depressant – Slurred speech – Energetic – Playful – Reduction in motor skills – Mild dizziness GHB TOXICITY

• MEDIUM DOSE (1-2.5 GRAMS) – Affectionate and sensual response – Increased erectile capacity – Heightened orgasm – Tactile sensitivity – Nausea and grogginess – Increased appreciation for music, dancing and/or talking GHB TOXICITY

• High dose (2.5 grams +) – Euphoria – Increased grogginess and nausea/vomiting • Overdose (greater than 2 grams) – Nausea and vomiting – Like other CNS depressant drugs( alcohol, heroin) – Seizure activity – Coma NOTE: Dose is hard to titrate so might quickly move from medium to overdose SALVIA DIVINORUM

• DIVINER’S SAGE • INDUCES DISSOCIATIVE STATES AND PRODUCER OF “VISIONS” AND OTHER HALLUCINATORY EXPERIENCES • SIERRA MAZATECA OF OAXACA, MEXICO • USED BY MAZATEC SHAMANS FOR RELIGIOUS AND SPIRITUAL HEALING SESSIONS SALVIA DIVINORUM SALVIA DIVINORUM SALVIA DIVINORUM SALVIA DIVINORUM SALVIA DIVINORUM PHARAMCOLOGY • ACTIVE INGREDIENT SALVINORUM A IS A POTENT K-OPIOID AND D2 RECEPTOR AGONIST • USUALLY SMOKED OFTEN WITH WATER PIPE • POTENT NATURALLY OCCURRING HALLUCINOGEN ALTHOUGHT DOES NOT SEEM TO WORK THROUGH THE SEROTONIN SYSTEM SALVIA DIVINORUM- SUBJECTIVE • POSITIVE – SHORT DURATION ESPECIALLY WHEN SMOKED – RADICAL PERSPECTIVE SHIFTING – INCREASE IN SENSUAL APPRECIATION – DREAMLIKE EXPERIENCES – INSIGHT INTO SELF • NEUTRAL – CHANGE IN BODY TEMPERATURE, FLUSHING – SENSATION OF ENTERING OR PERCEIVING OTHER DIMENSIONS SALVIA DIVINORUM- SUBJECTIVE • NEUTRAL (CONTINUED) – FEELING OF PRESENCE OR ENTITY CONTACT – DISSOCIATION AT HIGHER DOSES • NEGATIVE – OVERLY-INTENSE EXPERIENCES – FEAR, TERROR AND PANIC – MILD TO MODERATE HEADACHE – COORDINATION PROBLEMS KROKODIL

• RAMPANT ABUSE IN RUSSIA • MIXTURE OF CODEINE AND GASOLINE, PAINT THINNER, IODINE, HYDROCHLORIC ACID AND RED PHOSPHOROUS • DESOMORPHINE-SYNTHESIZED IN US IN 1932 • HEROIN-LIKE EFFECTS (8-10 stronger than morphine) • MUCH CHEAPER TO OBTAIN-CODEINE SOLD OTC IN RUSSIA KROKODIL PHARMACOLOGY

• Half-life short so have to inject every 90 -120 minutes • Short half-life means Acute Abstinence Syndrome comes on very quickly • Pharmacology similar to other opioids with typical subjective effects and acute abstinence syndrome KROKODIL KROKODIL KROKODIL KROKODIL KROKODIL KROKODIL

• Name comes from the appearance of the skin of chronic users and the derivative of codeine (chlorocodide) used in production • Severe tissue damage, phlebitis and gangrene • The amount of tissue damage is so severe the life expectancy of a chronic addict is only 3-4 years “JENKEM” (INHALANT)

• FERMENTATION OF HUMAN WASTE • FECES AND URINE STORED IN TIGHT CONTAINER FOR SEVERAL DAYS • REACTION PRODUCES METHANE GAS • “HUFFED” BY USERS TO CREATE ANOXIA