Psychedelics: Mescaline, PCP, and Salvinorin A PDF

PSYCHEDELICS Mescaline And Others  Mescaline Active ingredient in peyote cactus, San Pedro cactus, and Peruvian Torch cactus Isolated and named in 1897 by Heffler Synthesized in 1919 by Spath Used to treat illness and in religious and cultural ceremonies dating back t...

PSYCHEDELICS Mescaline And Others  Mescaline Active ingredient in peyote cactus, San Pedro cactus, and Peruvian Torch cactus Isolated and named in 1897 by Heffler Synthesized in 1919 by Spath Used to treat illness and in religious and cultural ceremonies dating back to the Aztecs Only psychedelic sanctioned for open use by US government (Native American Church)  Mescaline Entered Mainstream culture in the 1950s with publication of Huxley’s “The Doors of Perception” Widespread use in universities until LSD and laws introduced to control all psychedelics  Mescaline ADME Consumed orally Mescal buttons have nauseous odor and bitter taste Typical dose 200-500 mg/5-15 buttons Rapidly and completely absorbed Relatively long acting (4-12 hours) Structurally similar to norepinephrine but it acts on serotonin, type 2A receptors (agonist)  Mescaline Effects Similar effects as LSD but 1/2000th as potent 1st symptoms are: – Nausea, vomitting, tremors, incoordination After approx 1 hour: – Vivid hallucinations  Mescaline Tolerance and Dependence Tolerance develops rapidly Tolerance dissipates within approx. 7 days No physical dependence Minimal to no psychological dependence  Phencyclidine (PCP) General Info Synthetic Developed and marketed in 1963 as an analgesic and anesthetic Use discontinued in humans due to adverse reactions in recovery When medical use halted, it appeared on street under a variety of names e.g., crystal, angel dust, hob  PCP ADME Comes in various forms Administered orally, intra-nasally, intravenously, and via inhalation Long half life Many psychoactive metabolites Effects typically last 4-6 hours Effects followed by partial or total amnesia  PCP Mechanism of Action Antagonist of glutamate and aspartate at NMDA receptors Inhibit serotonin re-uptake Agonistic action at opiate and adenosine receptors  PCP Effects Dose of 5 mg – Euphoria – Slurred speech – Motor incoordination – Drowsiness – Numbness of extremities Dose of 10 mg or more – Increased hr and bp – Sweating, nausea – Pupil dilation  PCP Effects Dose of 10 mg or more – Analgesia – Changes in Body Image – Prolonged visual stare – Nystagmus – Blurred or double vision – Feeling detached from others/surroundings or their own body – Amnesia  PCP Effects Dose of 10 mg or more – Frenzied motor activity or Catatonic Stupor – Sudden mood changes – Disorientation, confusion – Delusional thought – Repetitive stereotyped movements Psychotic behavior disappears as drug levels decline but sometimes requires hospitalization  PCP Toxic Effects With high doses (20 mg) – Respiratory Depression – Generalized Seizures – Pulmonary Edema Fetal Effects – Use in pregnancy slows growth, precipates labor and causes fetal distress – Infants show muscle stiffness, tremor, irritability, and attention problems (latter can last several years) – Animal studies: widespread brain cell death  PCP Tolerance & Dependence With daily use, develops within 2-3 weeks Psychological dependence develops No clear evidence of withdrawal syndrome in humans  Salvinorin A General Info Psychoactive compound found in the mint plant “Salvia divinorum” (leaves contain about.18% Salvinorin A) Plant is indigenous in a region in Oaxaca, Mexico Traditionally used by Mazatec shamans for health purposes and spiritual healing purposes First reported in 1930s and psychoactive compounded identified in 1990  Salvinorin A General Info Recreational use saw a rise in popularity in the 21st century It is a Schedule IV drug in Canada Usage is relatively low, with highest rates in teens and young adults – 2009: 1.6 % aged 15 or older (7.3% in ages 15 to 24) – 2019: 2.2 % aged 15 or older (4.8% ages 20 to 24 vs 2.1 % ages 25+)  Salvinorin A ADME Administration – Oral Leaves chewed; held in mouth for 20 to 30 min Tinctures: drops into cheek Typical dose: 30 grams of fresh leaves – Smoked/Inhalation Dried leaves burned Dried leaves vaporized and aerosol mixture inhaled Typical dose: 250 to 750 milligrams  Salvinorin A ADME Rapidly distributed throughout body and quickly eliminated With oral admin – Effects felt within 5 – 10 minutes, build and plateau over another hour, and then begin to slowly decline after 60 minutes With smoking – Effects experienced within 30 seconds, peak in 5 to 10 minutes (2 minutes with vaporization) then gradually decline over 20 to 30 minutes  Salvinorin A ADME Cleared from the brain with an active transport mechanism Metabolized by the liver and gallbladder Principle metabolite is inactive  Salvinorin A Pharmacology Opioid Agonist at kappa receptors Animal studies suggest that it indirectly affects other neurotransmitter systems – Inhibiting release of dopamine in striatum, prefrontal cortex, and nucleus acumbens – Inhibiting release of serotonin in hippocampus – Stimulates release of NE in hippocampus  Salvinorin A Some Effects Physiological effects – Increased sweating – Body feeling warm/hot or “chills” – Dizziness – Nausea – Intense drooling – Decreased heart rate – Experiences of rotation  Salvinorin A Some Effects Behavioral – Impaired coordination – Uncontrollable laughter Psychological – Feeling calm, dreamy like state – Improved mood and self-confidence – Increased insight and creativity – Mind racing – Time distortions – Spirtual experiences  Salvinorin A Some Effects Psychedelic – Colourful visions of objects and designs – Perception of becoming an object – Changes in bodily form – Revisiting places from the past – Overlapping realities – “Salvia Winds”: feeling of intense sideways or downwards pressure  Salvinorin A Effects Effects not always pleasant Some adverse effects are – Headaches – Drowsiness – Dysphoria – Feeling of terror and panic attacks  Salvinorin A Tolerance and Dependence No evidence of tolerance Mild withdrawal symptoms – Headache, irritability, insomnia – Case study reported nausea, vomiting, diarrhea stomach pain that developed in 48 hours and persisted for 3 days