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Lecture Thirteen

Psychedelic Drugs

**What is a psychedelic drug? A drug that alters sensation and perception as its PRIMARY mode of action.
What are three specific types of psychedelics ? Hallucinogens, Enactogens, Entheogens
Most psychedelics are not addictive (physically reinforcing) as they do not activate reward pathways, but they can be ___________________ addictive psychologically --> from the experience
**List the 5 mechanisms of fatality (ways drugs can kill)** (test2 or exam question) 1) physiological depression 2) physiological excitation 3) Rare reaction (personal physiology doesn't react well) 4)Toxicity reaction (e.g. mixing alcohol and cocaine) 5) Mode of action of drug (may go crazy and jump out window or drink drive.
**What is an example of the mxn of fatality (1) physiological depression? Alcohol depresses respiratory system
**What is an example of the mxn of fatality (2) physiological excitation? too much of a psychostimulant such as cocaine can manifest into fatal seizure due to too much GABA or Glutamate.
**What is an example of the mxn of fatality (3) rare reaction? Drug called Onfi can cause cause rare but fatal skin reaction.
**What is an example of the mxn of fatality (4) toxicity reaction? Mixing alcohol and cocaine, HR goes up and down so cardiovascular risk!
**What is an example of the mxn of fatality (5) Mode of action? Alcohol makes you go crazy and drink drive. Or psychedelic PCP and Ketamine have analgesic mode of action so don't realise when seriously hurt yourself.
**Comment on the peak age of psychedelic age use. Peaks around 25-34 years. This is different to most other recreational drugs used mostly by younger teenagers. So different that older age-range experiment with psychedelic drugs.
**Comment on the ethnicity of psychedelic users Also different to other recreational drugs as with psychedelics more european/other ethnic groups use them than Maori, Pacific and Asian.
**Psychedelic effects show 3 key properties. What is #1? 1) Highly variable BETWEEN and WITHIN individuals. One person can have a highly dif. experience to another person (between) One person can have a highly dif. experience on friday to their experience on sunday (within)
**Psychedelic effects show 3 key properties. What is #2? 2) Largely susceptible to placebo, expectation and contextual effects AND personality effects (or Law of initial values) where we all have dif. personality to begin with so might have dif. experience to other based on your personality.
**Psychedelic effects show 3 key properties. What is #3? 3) Potentially lethal, not necessarily due to mxm of action but rather MODE of action (it can make you do crazy stuff like jump from high building window. But this doesn't always happen as the drug effects people differently.
** Scopolamine is a psychedelic drug. What is it derived from? What is its MXN of action? What is its MODE of action? Found/derived in certain plants and has synthetic versions. MXN of action is mACh receptor ANTAGonist. MODE of action is delerium (confused), intoxication, amnesia
**What are the three modes of action of Scopolamine? Delirium (confusion), intoxication, amnesia.
** Phsyciologically scopolamine is not pleasant. Why? Scop. is a mACh antagonist which means HR & BP incr. GI doesnt work well, decr. in secreations (saliva, tears, sweat). Scop. also contains Atropine which is a mAcH antagonist that blocks regular activity of parasympathetic NS -fatal both MOA and mode.
**So, what is the general mode of action of scopolamine? Deliriant
** What are the therapeutic uses of scopolamine? pupil dilatation for ophthalmology and motion sickness. (Using therapeutically for these does not give psychedelic effect as use extremely low doses)
**Where is LSD derived from? And who discovered and started investigating LSD? From ergot fungus. DR. Albert Hofmann
**LSD is very POTENT, given in what type of measurement? ug (micrograms)
**What is the mxn of action of LSD? What is the general mode of action? 5-HT2 receptor agonist. Hallucinogen
** What is Mescaline derived from? Certain cacti and there are synthetic versions
**What is the mxn of action of Mescaline? What is the mode of action? 5-HT2 receptor agonist, Hallucinogen and entheogen is usually derived from the hallucinogen component.
**What is Psilocybin + Psilocin derived from? Certain fungi
**Why is the type of mushroom that we get Psikocybin + Psilocin, important? Because some are more potent than others, Some are not psychedelic and are actually toxic mushrooms that look like magic mushrooms.
**What is the mxn of action and mode of action of Psilocybin + Psilocin? MOA: 5-HT2 receptor agonist. And mode is hallucinogen.
**With respect to tolerance of Psychedelic drugs, LSD, Mescaline and Psilocybin/Psilocin exhibit both tolerance and ________-tolerance. What happens to cause tolerance? cross, downregulation of 5-HT2 receptors.
**What does cross-tolerance mean? if you take LSD on Friday, and then Mescaline on Saturday and then Psilocin on Sunday, you dont have effect on Sunday. Because all of these drugs activate the same 5-HT2 receptors, they all cause downregulation so no more left by Sunday
**Comment on dependence/addiction of psychedelic drugs Lab animals do NOT self-administer/seek them and humans do not report strong reinforcing effects (no need to take drug again) so no PHYSICAL dependence BUT might have psychological addiction as pleasant experience that they want again and again.
**List the 4 biggest adverse effects with serotonergic psychedelics. 1)Bad trips(even if 1st 20 times are pleasant 21st time is unpleasant) 2)Exacerbation of psychosis or depression 3) Hallucinogen Persisting Perceptual Disorder(HPPH=flashbacks even years later) 4) Disruption of Personality(burnout,flattened affect, voice)
**What is the Amphetamine Derivative Psychedelic drug we are going to focus on? MDMA (ecstacy)
**Comment on the dose-dependent effects of Amphetamine derivative psychedelics such as MDMA. There is a shift in mode of action with dose. At low dose there is a stimulant effect. At medium dose, there is psychedelic/enactogen effects. At high dose there is tremors, conculsions or death.
**At a low dose of Amphetamine derivative psychedelics such as MDMA, what do we normally experience? Stimulant effects
**At a medium dose of Amphetamine derivative psychedelics such as MDMA, what do we normally experience? Psychedelic/enactogen effects
**At a high dose of Amphetamine derivative psychedelics such as MDMA, what do we normally experience? tremors, convulsion, or death
**Amphetamine Derivatives are s_____________? What is the mxn of action for amphetamine derivatives? synthetic. MOA: prompts vesicular release of DA, NE, 5-HT. Is also a mixed DA/5-HT receptor agonist.
**What is the general mode of action of Amphetamine derivatives? Stimulant + psychedelic/enactogen
**Comment on the two side effects of Amphetamine Derivative Psychedelic drugs. 1)Sympathomimetic effects (high BP/HR,jaw clenching, restlessness,insomnia,impaired gault,convulsions-probs hav frm party envir. so exacerbated by drug) 2)Growing evid. of neurological dam.(attent&memory deficits, incr.impulsivity, reduced 5-HT turnover
**In the lab MDMA (amphetamine derivative psychedelic drug) is used as a potent and selective neurotoxin to kill 5-HT neurons. So if MDMA kills 5-HT in petri dish this gives concern to what it is doing in our brain! **
**What are PCP and Ketamine drugs derived from? They are synthetic, not plant based
**What can you comment about the ROA of PCP and Ketamine? That they have more serious ROA such as snorting, smoking, injecting so are harder drugs
**What is the mxn of action for PCP and Ketamine? Mode of action? NMDA receptor antagonist. Mode of action is a Dissociative.
**What does the mode of action of PCP and Ketamine, dissociative, mean? = Inducing an altered level of consciousness - dissociated from the body
**What are the therapeutic uses of PCP and Ketamine? Limited anaesthesia use (not 1st line anaesthetic).also used as off-label pain management and off-label depression which is illegal.
**Comment on the the seriousness of a high dose of PCP and Ketamine can cause coma and has lethality
**Comment on the dependence/addiction of PCP and Ketamine They are the only psychedelic drug that animals will self-administer and exhibit withdrawal from (consistent with the compulsive use patterns seen in humans). They also exhibit overdose potential due to their long half-life of metabolites (24-48hrs)
**Dextromethorphan is s________ and with respect to ROA, requires ________ doses to get a psychedelic effect synthetic, high
**What is the mxn of action for Dextomethorphan? Mode of action? NMDA receptor antagonist (DXM and metabolite DXO). Mode of action: With high doses only it causes a dissociative effect from self and environment
**What is the therapeutic use of Dextromethorphan? Analgesic adjunct
Created by: alice476