1. MIND ALTERING DRUGS MIND ALTERING… SYNTHETIC (DESIGNER) AND NATURALLY OCCURING…DRUGS Cardwell C. Nuckols, PhD cnuckols@elitecorp1.com www.cnuckols.com (407) 758-1536

2. DESIGNER DRUGS HELPFUL SITES WWW.DESIGNERDRUGTRENDS.ORG WWW.EROWID.ORG

3. DESIGNER DRUGS The largest percentage of new chemicals found in US drug busts are synthetic cannabinoids Synthetic cathinones permutations of the cathinone molecule made by the khat plant Catha edulis come in second

4. WWW.DESIGNERDRUGTRENDS.ORG

5. TEN MOST DEADLY STREET DRUGS 1. Krokodil 2. Whoonga 3. Bath salts 4. Crack cocaine 5. Heroin 6. Flakka 7. AH-7921 8. Crystal meth 9. Purple Drank 10. Scopolamine

6. PHARMACOLOGICAL CATEGORIES STIMULANT DRUGS – “BATH SALTS” – KHAT (CATHINONE) CANNABINOIDS – “SPICE” AND A WIDE VARIETY OF CANNABINOID RECEPTOR AGONISTS DEPRESSANTS – GHB

7. 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 – NBOMes 25I-MBOMe (N-bomb) – SALVIA DIVINORUM – “FOXY METHOXY”

8. PHARMACOLOGICAL CATEGORIES OPIOIDS – KRATOM (7-HYDROXYMITRAGYNINE) – KROKODIL (DESOMORPHINE) INHALANTS – JENKEM ARYLCYCLOHEXYLAMINES – KETAMINE – METHOXETAMINE (MXE)

9. STIMULANT DRUGS IN GENERAL Methamphetamine Cocaine Nicotine Caffeine Routes of Administration – Oral – IV – Pulmonary

10. STIMULANT TOXICITY Increased levels of Norepinephrine and Dopamine – Hyper-arousal – Pleasure – Paranoia Increased levels of Serotonin – Reduced hunger – Difficulty sleeping

11. STIMULANT CRASH Reduced levels of Norepinephrine and Dopamine – Dysphoria – Depression – Anhedonia Reduced levels of Serotonin – Mood swings – Sleep disturbances

12. ACUTE ABSTINENCE SYNDROME Reduced Noradrenergic activity 1 to 4 days – Low stimulant craving – High carbohydrate craving 4 to 10 days – Free floating anxiety – Euphoric dreams – Drug cravings

13. “BATH SALTS” AND RELATED STIMULANTS In the 1970s, a medicinal chemist named Richard A. Glennon was studying what it would take to convert a stimulant drug to a hallucinogen and vice versa in order to determine how these substances work in the brain. He knew that small modifications to a drug's molecular structure could result in major changes in its effects. By introducing an oxygen atom to the side chain of amphetamine, he created something called a beta-keto amphetamine. Beta-keto amphetamine was what we now call cathinone. Richard A. Glennon

14. “BATH SALTS” AND RELATED STIMULANTS

20. 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)

21. “BATH SALTS” AND RELATED STIMULANTS ‘Meow meow', officially known as mephedrone and now illegal, is just one of a group of drugs called Novel Psychoactive Substances (NPS), which also includes the amphetamine-like substances Benzo Fury and PMA, amongst others. In the UK, the prevalence of these drugs in the post mortem toxicology tests submitted to the report has increased 800% in three years, from 12 in 2009 to 97 in 2012 University of St George's London. "Growing impact of lethal 'legal highs:' U.K. Deaths report." ScienceDaily, 11 February 2014.

22. “BATH SALTS” AND RELATED STIMULANTS Taking bath salts, it seemed, was similar to taking amphetamine and cocaine at the same time. Except for one thing: MDPV is as much as 10 times stronger than cocaine.

23. “BATH SALTS” AND RELATED STIMULANTS Block the reuptake of dopamine, norepinephrine and serotonin Mephedrone favors dopamine reuptake inhibition Doses of 100-200mg typically ingested orally with action in 30-45 minutes Rush peaks at 90 minutes and lasts 3-4 hours with entire experience lasting 6-8 hours

24. “BATH SALTS” AND RELATED STIMULANTS Mephedrone is regarded as an analog of 3,4 methylenedioxy-N-methylamphetamine (MDMA) Both increase talkativeness and sexual arousal They are “entactogens” causing a person to emotionally identify with or feel connected to another most likely due to increased serotonin

25. “BATH SALTS” AND RELATED STIMULANTS Compared to amphetamines (8-10 hours of action), some of the cathinone's have a duration of effect up to 24-48 hours with many users reporting agitated delirium or psychosis for weeks after ingestion Extreme psychiatric features known to occur after initial use Cathinone's have higher prevalence of seizure disorder

26. “BATH SALTS” AND RELATED STIMULANTS MDPV is already widely considered one of the worst-ever drugs in terms of addiction potential. In a study reported in 2013, for example, the Taffe and Dickerson labs showed that MDPV induced far more drug- seeking lever presses in rats than crystal meth

27. “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

28. “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

29. “BATH SALTS” AND RELATED STIMULANTS TRADE NAMES-SOLD AS PLANT FOOD AN DFOR 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

30. “BATH SALTS” AND RELATED STIMULANTS

31. FLAKKA It's smoked or vaped, snorted, injected, and swallowed Also called “gravel" because it looks like the colorful gravel pebbles you'd use to decorate the bottom of an aquarium. Flakka is made from a compound called alpha-PVP, a chemical cousin of cathinone, the amphetamine- like drug found in bath salts.chemical cousin of cathinone, the amphetamine- like drug found in bath salts Excessive use has been linked with feelings of extreme anxiety, paranoia, and hallucinations

32. FLAKKA At high doses, flakka may also cause the body to reach high temperatures (bath salts have been linked with the same symptom). This excessive temperature can lead to severe physical complications like kidney damage and muscle breakdownbath salts have been linked with the same symptom Flakka can cost as little as $5 a pop$5 a pop

33. FLAKKA Alpha-PVP (α-pyrrolidinopentiophenone) is a synthetic stimulant; the street drug supply is reportedly made in laboratories in China, India and Pakistan. It was designed to be slightly different, chemically, from MDPV, which has been illegal in the U.S. since 2011. The new drug's chemical difference, the lack of a cluster of atoms known as the 3,4-methylenedioxy motif, is the same as the one that distinguishes methamphetamine from MDMA ("Ecstasy"). Alpha-PVP was legal until the U.S. Drug Enforcement Administration put a ban on it early in 2014 -- a temporary ban that is almost certain to become permanent.

34. FLAKKA

36. 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

37. KHAT PHARMACOLOGY EUPHORIANT (DOPAMINE) ANOREXIGENIC STIMULANT – DILATED PUPILS – INCREASED HEART RATE – INCREASED BLOOD PRESSURE HYPNAGOGIC (AUDITORY DREAM LIKE) HALLUCINATIONS (COMING DOWN)

38. KHAT

39. KHAT

40. KHAT

41. KHAT

42. KHAT

43. KHAT

44. BETEL NUTS The betel nut, a seed of the areca palm, is grown and used throughout India, parts of China and much of Southeast Asia, including Indonesia and most of the Pacific islands. Chewing the betel quid -- a mixture of areca nut, spices and slaked lime wrapped in betel vine leaves -- has been a cultural tradition in those regions for centuries. In small doses, it creates a sense of euphoria and alertness. Prolonged use can create addiction and the World Health Organization classifies the betel nut as a carcinogen.

45. BETEL NUTS The nut's active ingredient, arecoline, acts on the same receptor proteins in the brain as nicotine Roger L. Papke, Nicole A. Horenstein, Clare Stokes. Nicotinic Activity of Arecoline, the Psychoactive Element of "Betel Nuts", Suggests a Basis for Habitual Use and Anti-Inflammatory Activity. PLOS ONE, 2015; 10 (10): e0140907 DOI: 10.1371/journal.pone.0140907 10.1371/journal.pone.0140907

46. BETEL NUTS

47. BETEL NUT SMILE

48. CAPTAGON Captagon (fenethylline) was first developed in the 1960s as a treatment for hyperactivity, narcolepsy, and depression. But by the 1980s the drug was banned in most countries due to its extremely addicting properties. Sometimes referred to as a “smart drug” or “nootropic,” Captagon acts like most amphetamines, giving users a euphoric sensation, making them more talkative, staving off sleep and hunger, and providing a burst of energy

49. CAPTAGON Captagon is widely abused by Syrian soldiers on both sides of the civil war to keep them awake, alert, and, more concerningly, addicted. Although users believe the drug bestows them with “special powers

50. “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)

51. 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 (100-800 times more potent than THC) – WIN 55,212-2

52. CANNABINOID EFFECTS Appetite, feeding behavior and body weight Reward and motivation Mood and anxiety Pain Memory

54. 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

55. RIMONABANT Clinical Trials – Test subjects No psychiatric history No family history – High Drop-out rate – Psychiatric Side-Effects Anxiety Depression BRAINWORK (May-June 2006)

56. 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

57. 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.

58. 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.

59. 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.

60. 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.

61. SYNTHETIC CANNABINOIDS (SPICE)

62. SYNTHETIC CANNABINOIDS

66. SYNTHETIC CANNABINOIDS { SYNTHETIC CANNABINOIDS {K2 (JWH- 018, JWH-073)}

67. “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

68. “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

69. “SPICE” AND OTHER SYNTHETIC CANNABINOIDS The first case of catatonic psychosis caused by a synthetic derivate of Cannabis, Spice, has been described by researchers. The relation between the consumption of this substance, a psychotic break and some locomotor system problems, similar to the ones caused by Parkinson's, have also been described for the first time.

70. “SPICE” AND OTHER SYNTHETIC CANNABINOIDS Until now, recent studies had already shown the relation between the spice and different types of psychosis, but this is the first clinical case described on an international scale in which the psychotic break appears with abnormal movements. The movement disorder detected in this case, similar to catatonia, consists in the loss of harmony in the walking process and neck, arms and head stiffness

71. “SPICE” AND OTHER SYNTHETIC CANNABINOIDS The other relevant aspect is that the motor symptoms and the bent-over posture of "mantis religiosa" persisted even months after stopping the consumption. Gonzalo Haro, Carmen Ripoll, María Ibáñez, Teresa Orengo, Víctor M. Liaño, Emilio Meneu, Félix Hernández, Francisco Traver. Could Spice Drugs Induce Psychosis With Abnormal Movements Similar to Catatonia? Psychiatry: Interpersonal and Biological Processes, 2014; 77 (2): 206 DOI:10.1521/psyc.2014.77.2.20610.1521/psyc.2014.77.2.206

72. “SPICE” AND OTHER SYNTHETIC CANNABINOIDS

73. BHANG Bhang has been used in India since Vedic times, and is an integral part of North Indian culture. Sadhus and Sufis use bhang to boost meditation and to achieve transcendental states. Bhang or cannabis is also used amongst Sufis as an aid to spiritual ecstasy.

74. BHANG Using mortar and pestle, the buds and leaves of cannabis are ground into a paste. To this mixture, milk, ghee (made from butter) and spices are added. The bhang base is now ready to be made into a heavy drink, thandai, an alternative to alcohol. Bhang is also mixed with ghee and sugar to make a purple halva (dense sweet confection), and into peppery, chewy little balls called 'golee' (which in this context means candy or pill in Hindi)

75. BHANG

76. 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

77. 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

78. GHB

79. GHB

80. GHB

81. GHB

82. 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

83. 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

84. GHBTOXICITY 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

85. GHB ACUTE ABSTINENCE SYNDROME Initially feel drowsy, groggy and sleepy as the “morning after” effects The AAS includes… – Insomnia – Anxiety and tremor – Resolved in 3-12 days – Prolonged and difficult

86. HALLUCINOGENS 2C-E NICKNAMED “EUROPA” SYNTHESIZED IN 1970’S-1980’S PSYCHEDELIC PHENETHYLAMINE 4-ETHYL-2,5 DIMETHOXYPHENETHYLAMINE TAKEN ORALLY POWERFUL HALLUCINOGENIC EFFECTS HIGH LASTS 4-9 HOURS SOLD THROUGH EUROPEAN SOURCES

87. 2C-E NICKNAMED “EUROPA” SYNTHESIZED BY ALEXANDER SHULGIN POPULARIZED MDMA (ECSTASY) PIHKAL BOOK (1991) – PHENETHYLAMINES I HAVE KNOW AND LOVED 2C-I ANOTHER PHENETHYLAMINE IS AVAILABLE 2C-E IS SCHEDULE I

88. PHENETHYLAMINES I HAVE KNOW AND LOVED

89. VIAL OF 2C-E

90. CHEMICAL CONFIGURATION

91. PACKET OF 2C-E

92. 2C-E POWDER

93. 2C-E PHARMACOLOGY TOTAL DURATION 4-9 HOURS ONSET 20-90 MINUTES PLATEAU 3-7 HOURS COMING DOWN 1-2 HOURS AFTER EFFECTS 2-4 HOURS HANGOVER 6-24 HOURS

94. 2C-E PHARMACOLOGY: SUBJECTIVE EXPERIENCE POSITIVE – SENSE OF WELL-BEING – MENTAL AND PHYSICAL STIMULATION – INCRESED AWARENESS OF SENSES – VISUAL EFFECTS – SPIRITUAL EXPERIENCES – INCREASE IN CREATIVE THINKING

95. 2C-E PHARMACOLOGY: SUBJECTIVE EXPERIENCE NEUTRAL – PUPIL DILATION – CONFUSION – DIFFICULTY CONCENTRATING – CHANGE IN TIME PERCEPTION – INCREASE IN BODY TEMPERATURE – SLIGHT INCREASE IN HEART RATE

96. 2C-E PHARMACOLOGY: SUBJECTIVE EXPERIENCE NEGATIVE – MUSCLE TENSION AND ACHING – JAW TENSION – INCREASED PERSPIRATION – NAUSEA AND VOMITING – DIZZINESS AND CONFUSIION – PARANOIA – DIFFICULTY INTEGRATING EXPERIENCE

97. MDMA 3,4 methylenedioxy-methamphetamine Ecstasy, XTC Synthetic psychoactive drug similar to both the stimulant drug methamphetamine and the hallucinogen mescaline Introduced in the 1970’s as an aid in psychotherapy Initially popular with the adolescent and young adult population but now has a broad audience “Raves”

98. MDMA-SUBJECTIVE EXPERIENCE Increased energy Euphoria Emotional warmth Empathy towards others Distortions in sensory and time perception Usually taken orally as a tablet or capsule Some gay and bisexual men use MDMA mixed with cocaine, GHB, methamphetamine, ketamine and sildenafil (Viagra)

99. MDMA PHARMACOLOGY Methamphetamine breakdown product – Sympathetic Nervous System (Sympathomimetic) Increased heart rate Increased blood pressure Dilated pupils Perspiration Reduced hunger and thirst – Hallucinogenic Sensory hallucinations

100. MDMA PHARMACOLOGY Increases the activity of… – Serotonin – Norepinephrine – Dopamine Serotonin triggers the release of oxytocin and vasopressin – Love – Trust – Sexual arousal

101. There are at least two sides to the neurotransmitter story Sex Appetite Aggression Concentration Interest Motivation Depressed Mood Anxiety Irritability Thought process Norepinephrine (NE) Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms Serotonin (5-HT) Vague Aches and pain Functional domains of Serotonin and Norepinephrine 1-4

102. MDMA

103. MDMA

104. MDMA

105. MDMA

106. MDMA

107. MDMA TOXICITY Dehydration Hyperthermia Increased ANS functioning – Seizures Heart and kidney failure “Stacking and combining” Serotonin damage

108. MDMA WITHDRAWAL Acute Abstinence Syndrome – Pale – Dysphoric – Depressed – Confusion and anxiety – Somnolent – Paranoia(can last for weeks)

109. MDMA MEDICAL MANAGEMENT Benzodiazepines(Ativan) – Sedation, muscle relaxation and seizure management Benzodiazepines(Valium) – Depresses the CNS Anticonvulsants(Dilantin) Barbiturates(Phenobarbital) – Anticonvulsant when Benzo and Dilantin fail

110. MDMA MEDICAL MANAGEMENT Antihypertensives (Regitine) – Lower blood pressure GI Decontaminate – Activated charcoal Absorbs MDMA and limits absorption

111. NBOMes 25I-NBOMes N-Bombs Psychedelic that can produce delirium, paranoia, violence, seizures, racing heart and spiking blood pressure Chemically resemble mescaline Masquerades as extra serotonin which plays a role in mood and aggression

112. NBOMes Can be dissolved and sold on paper blotters – Often sold as LSD One of the bizarre effects is that people will stab themselves and/or others Can create a long-term state of agitated delirium reported up to five days

113. NBOMes

115. 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

116. SALVIA DIVINORUM

120. SALVIA DIVINORUM PHARAMCOLOGY ACTIVE INGREDIENT SALVINORUM 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

121. SALVIA DIVINORUM-SUBJECTIVE POSITIVE – SHORT DURATION ESPECIALLY WHEN SMOKED Minutes to 1 hour – RADICAL PERSPECTIVE SHIFTING – INTENSE HALLUCINATIONS – INCREASE IN SENSUAL APPRECIATION – DREAMLIKE EXPERIENCES – INSIGHT INTO SELF NEUTRAL – CHANGE IN BODY TEMPERATURE, FLUSHING – SENSATION OF ENTERING OR PERCEIVING OTHER DIMENSIONS

122. SALVIA DIVINORUM-SUBJECTIVE NEUTRAL (CONTINUED) – FEELING OF PRESENCE OR ENTITY CONTACT – DISSOCIATION AT HIGHER DOSES NEGATIVE – OVERLY-INTENSE EXPERIENCES – FEAR, TERROR AN DPANIC – MILD TO MODERATE HEADACHE – COORDINATION PROBLEMS

123. SALVIA DIVINORUM Possible antidepressant effect following intense hallucinations Marked absence of physiological effects such as heart rate and blood pressure Addiction is not a prominent feature Called Diviners Sage, Maria Pastora, Magic Mint and Mystic Sage

124. PIPERAZINES Drugs with varying properties often used in combination to mimic MDMA intoxication Most prevalent are –benzylpiperazine (BZP) and 1-(3-triflioromethylphenyl) piperazine (TFMPP) BZP is a weak amphetamine-like stimulant that is dopamine mediated and can cause motor abnormalities

125. PIPERAZINES TFMPP is a serotonin-mediated hallucinogen that both modifies and is synergistic with BZP Together TFMPP blunts the motor effects of BZP creating an MDMA-like effect Together serve as an entactogen Sold as Benzo Fury, Head Rush, MDAI, Exotic Super Strong, XXX Strong as Hell

126. PIPERAZINES SYNTHETIC MARKETED AS MOLLY

127. “FOXY METHOXY” 5-mEo-dissopropyltryptamine (5-MeO-DIPT) Tryptamine/alkyltryptamine family Closely related to DMT (“businessman’s lunch”) Targets 5-HT receptors

128. “FOXY METHOXY” CRYSTALS

129. “FOXY METHOXY” IN BLUE GELATIN CUBES

130. KRATOM (OPIOIDS) LEAF FROM LARGE TREES NATIVE TO SOUTHEAST ASIA MITRAGYNA SPECIOSA FOUND IN – MALAYSIA – THAILAND – INDONESIA ITHANG, BIAK BIAK, KETUM, KAKUAM, THOM

131. KRATOM TREE

132. KRATOM LEAF

133. KRATOM CAPSULES

134. KRATOM POWDER 2 GRAMS $60 (10-20 DOSES)

135. KRATOM RESIN EXTRACT 1 OUNCE=$60

136. Journal of Psychoactive Drugs Vol. 20 (No 4) 1988...leaves of Mitragyna speciosa, tree of Malaysia and Thailand, used as opium substitute, methods included tea, smoking and chewing. Found to suppress opiate withdrawal syndrome. Chronic users said to have darkened skin. Said to have both stimulating and depressant qualities as if chewing coca leaves and smoking opium simultaneously. Large doses lead to stupor. Withdrawal said to be considerably milder than that with the opiates. Mitragynine is thus a drug with a highly unusual but never the less well-documented history of being described as both a stimulant and depressant while at the same time possessing the chemical structure one might expect of a psychedelic. The Thai narcotic book described Kratom as weaker than morphine and less harmful than cocaine.

137. KRATOM PHARMACOLOGY MITRAGYNINE – 7-HYDROXYMITRAGYNINE (MAIN ACTIVE INGREDIENT) – SIMILAR IN STRUCTURE TO PSYHEDELICS BUT HAS NO REAL PSYCHEDELIC EFFECTS – INTERACTS WITH OPIOID RECEPTORS LOW DOSE-ATTACHES TO DELTA OPIOID RECEPTOR HIGHER DOSES-ATTACHES TO MU OPIOID RECEPTOR

138. KRATOM PHARMACOLOGY 7-HYDROXYMITRAGYNINE – POTENT OPIATE AGONIST – NATURAL CEILING EFFECT LIMITS EUPHORIA LIMITS RESPIRATORY DEPRESSION LIMITS OD POTENTIAL – NO KNOWN FATAL OD

139. KRATOM PHARMACOLOGY USED IN TREATMENT OF OPIATE DEPENDENCE – 1897, EUROPEANS BELIEVE LEAVES OF THE PLAN TO BE A CURE FOR OPIATE DEPENDENCE – CURRENTLY, USED FOR METHADONE DETOXIFICATION IN SOME COUNTRIES (EX. NEW ZEALAND) AND IN THAILAND TO DETOX AND MANAGE HEROIN ACUTE ABSTINENCE SYNDROME (AAS) – TO PREVENT ONSET OF AAS SYMPTOMS

140. KRATOM PHARMACOLOGY SEEMS TO BE… – A STIMULANT AT LOWER DOSES (MITRAGYNINE) – A SEDATIVE AT HIGHER DOSES (7- HYDROXYMITRAGYNINE) ONSET OF ACTION: 5-10 MINUTES DURATION OF ACTION: SEVERAL HOURS

141. KRATOM PHARMACOLOGY SHORT TERM EFFECTS: – DRY MOUTH – INCREASED OR REDUCED URINATION – LOSS OF APPETITE – NAUSEA/ VOMITING INTERMEDIATE EFFECTS – ANOREXIA WITH WEIGHT LOSS – INSOMNIA – DEPENDENCE

142. KRATOM PHARMACOLOGY LONG TERM HIGH DOSE EFFECTS – NERVOUSNESS – SLEEPLESSNESS – LOSS OF LIBIDO – CONSTIPATION – DARKENING OF SKIN

143. KRATOM PHARMACOLOGY OVERDOSE – RESPIRATORY DEPRESSION – DELUSIONS – LISTLESSNESS – TREMORS – AGGRESSION – NAUSEA

144. KRATOM PHARMACOLOGY ACUTE ABSTINENCE SYNDROME – SIMILAR TO OPIOIDS AROUSED SYMPATHETIC NERVOUS SYSTEM – INCREASED HEART RATE – INCREASED BLOOD PRESSURE – DILATED PUPILS – TREMORS CASE OF BODY FLU – MUSCLE ACHES – NAUSEA/VOMITING

145. AH-7921 Also known as doxylam In the commonly used name AH-7921, ‘AH’ refers to ‘Allen & Hanburys’, the company that patented the drug AH-7921 is an opioid analgesic drug selective for the µ-opioid receptor. Its effects are similar to that of morphine; although, AH- 7921 was found to produce stronger respiratory depression than morphine in mice.morphine

146. AH-7921 Routes of administration for AH-7921 include nasal, oral, sublingual, intravenous injection, vapor, and rectal administration In 2013, AH-7921 was discovered to have been used as an active ingredient in “synthetic cannabis” products in Japan

147. PURPLE DRANK Purple Drank is a mixture of a prescription cold medication with a soda drink like Sprite or Mountain Dew, plus ice and Jolly Rancher candies often added for color and taste. The cold medication should contain promethazine (an antihistamine) and codeine. These ingredients combined make a purple liquid that is then sipped until euphoria and dissociation from one’s body occur. These effects will last between three and six hours.

148. PURPLE DRANK It is common for the high associated with this combination to be called a “swooning euphoria.” The combo also has a sedative effect and makes a person woozy It is possible to take an overdose of codeine when abusing Purple Drank, resulting in an opiate overdose and death. If the use of the drink is combined with alcohol or other drugs, the combination can also contribute to death

149. PURPLE DRANK Among rappers and football players, there have been a number of arrests and deaths related to this drug combination. Most famously, rapper Lil Wayne talks and raps about use of this drink, as does the group Three Six Mafia. At least three hip hop rappers or producers have died, including DJ Screw and musician Big Hawk, both from Houston

150. 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

151. 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

152. KROKODIL

153. KROKODIL

154. KROKODIL

155. KROKODIL

156. KROKODIL

157. 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

158. “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

159. ARYLCYCLOHEXYLAMINES KETAMINE – DERIVATIVE OF PHENCYCLIDINE (PCP) – SHORT-ACTING GENERAL ANESTHETIC – SPECIAL K OR VITAMIN K – MODERATE TO HIGH DOSES PRODUCES HALLUCINATIONS AND OUT-OF-THE-BODY EXPERIENCES – “K-LAND” (A MELLOW HOUR LONG TRIP) AND “K- HOLE”(NEAR-DEATH OR CATATONIC EXPERIENCES) – DATE RAPE DRUG

160. ARYLCYCLOHEXYLAMINES METHOXETAMINE (MXE) – DERIVATIVE OF KETAMINE – ANESTHETIC USED IN “CLUB DRUG” SCENE – HAS HALLUCINOGENIC AND DISSOCIATIVE EFFECTS – TYPICALLY MORE POTENT AND LONGER ACTING THAN KETAMINE

161. ARYLCYCLOHEXYLAMINES METHOXETAMINE (MXE) – 2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone; 3- MeO-2-Oxo-PCE – Three patients aged between 28 and 42 years presented to the Emergency Department (ED) on unrelated occasions having used methoxetamine. Clinical features were suggestive of a "dissociative/catatonic" state similar to that seen with ketamine; in addition, they had clinical features of acute sympathomimetic toxicity with significant tachycardia and hypertension. All were managed with low-dose benzodiazepines and discharged home once their symptoms/signs had settled.

162. METHOXETAMINE (MXE)

164. WHOONGA In South Africa, two mainstay HIV drugs have found their way into recreational use. That may help explain why some HIV patients are resistant to these front-line medicines even if they've never been in treatment before an illicit concoction of an AIDS medication and a street drug, like marijuana or heroin Users crush tablets of the antiretroviral medication and mix the powder with other drugs for smoking

165. WHOONGA Use of efavirenz (sold as Sustiva in the U.S.) may exploit the HIV drug's well-known tendency to cause especially vivid and colorful dreams and other central nervous system effects. Hypothetically, that could enhance the effects of marijuana, methamphetamine, heroin and other illicit drugs.efavirenz Another HIV medication, ritonavir, (brand name Norvir) is believed to boost or prolong the effect of some street drugs, such as MDMA or Ecstasy.ritonavir