Lecture 11/12- Hallucinogens Flashcards
What are Hallucinogens?
Induce an altered state of consciousness, characterized by distortions of perception, hallucinations or visions, ecstasy, dissolution of self-boundaries and the experience of union with the world.
What can hallucinogens also be refered to as?
‘Psychedelics’ (mind revealing/opening)
What are the 2 types of Hallucinogens?
Classic hallucinogens
Dissociative anaesthetics
What are Classic hallucinogens?
Plant derived substances eg psilocybin (mushrooms) and mescaline (peyote cactus).
-Agonists at serotonin (5-HT) receptors. -Altered state of consciousness is primary effect
What are dissociative anaesthetics?
Synthetic drugs eg ketamine
-Produce anaesthesia (loss of sensation) at higher doses and altered states of consciousness at lower doses incl dissociation from environment.
-Non-competitive NMDA receptor antagonists.
What are the 5 primary dimensions with sub dimensions?
-Oceanic boundlessness
-Anxious ego-disintegration
-Visionary restructralisation
-Acoustic alterations
-Altered vigilance
What is Oceanic boundlessness?
Positively experienced loss of ego boundaries
eg Insightfulness, unity
What is anxious ego-disintegration?
Thought disorder and loss of self-control
eg Anxiety, impaired control
What is visionary restructrialisation?
Referring to perceptual alterations (visual illusions and hallucinations) and altered meaning of precepts
What is acoustic alterations and altered vigilance?
Hypersensitivity to auditory hallucinations
Why is it important to set expectations in subjective experience?
Psychopharmacological actions of hallucinogenic drugs may be less predictable than those of other drugs.
What are hallucinogenic effects dependent on?
The user’s expectations and the environment.
Eg expectations and environments that would foster religious or spiritual experiences increase the probability of the drug producing such an effect.
What do studies by Stanislav Grof (1975) and Barr et al (1972) suggest?
That an individual’s response to repeated administration of the same drug and dose may vary.
What is the historical background of hallucinogens?
-Have a longer history esp as part of ancient rituals
-Plant-derived hallucinogens and LSD entered Northern American and European mainstream culture in first half of 20th century. -PCP developed as anaesthetic in mid 1950s and ketamine synthesized as safer alternative in 1962 (still used as anaesthetic in humans)
How are hallucinogens used in research?
-Significant interest in researchers in understanding hallucinogenic drug actions and to exploit them clinically (either for mechanisms of altered states of consciousness or therapy use). -Ketamine approved as depressions treatment in US in 2019
What is Ecstasy (MDMA)
An amphetamine with strong effects on serotonin transmission
What properties does Ecstasy (MDMA) have?
-Has stimulant properties eg increasing alertness and ‘energy’
-Hallucinogenic-like properties which increase sociability and talkativeness which induces an ‘altered state on consciousness with emotional and sensual overtones’
How harmful are hallucinogenic drugs and MDMA?
Apart from potential distress caused by the subjective experiences induced by classical hallucinogenic drugs, these drugs cause otherwise virtually no physical harm and no dependence.
What can ecstasy and dissociative anaesthetics (Ketamine) cause?
What is the number of ecstasy related deaths?
Dependence and cause neurodegeneration, although it is debated if typical recreational usage and doses cause neurodegeneration.
130 in England, Wales, Scotland (2017)
What are the UK drug regulations?
Three Classes (A, B and C) to determine the penalties for offences such as supply, production and possession of a controlled drug.
Five schedules regulate the clinical use of controlled substances and their storage and labelling requirements.
What hallucinogens activate the serotonin (5HT2) receptors?
Indoleamine and phenethylamine hallucinogens
How does the serotonin system link to hallucinogens?
Serotonergic raphe nuclei in the midbrain innervate large parts of the brain, including many cortical and subcortical forebrain regions.
How does 5HT2A receptors link to hallucinogens?
-5HT2A receptors are G protein-coupled receptors; their activation mainly has stimulatory effects on the neuron (increased transmitter release and increased activity).
-5HT2A receptor activation may stimulate excitatory neurons, including in the prefrontal cortex, which may be critical for the hallucinogenic effects
How does MDMA (ecstasy) simulate serotonin release?
Stimulates serotonin release (probably by interaction with 5HT transporter) and some of MDMA’s subjective effects are mediated by 5HT2A receptors.
How does MDMA (ecstasy) affect dopamine release?
Also stimulates dopamine release, including in nucleus accumbens, which is thought to contribute to stimulant and rewarding/reinforcing properties
What are the 3 adverse effects of dissociative anaesthetics?
Dependence
Neurodegeneration
Ketamine-induced ulcerative cystitis
What is Dependence regarding adverse effects of dissociative anaesthetics and MDMA?
Evidence from animal models and humans supports that both dissociative anaesthetics (ketamine, PCP) and MDMA can cause dependence, although the potential for dependence may be weaker than with other drugs of abuse eg opioids
What is Neurodgeneration regarding adverse effects of dissociative anaesthetics and MDMA?
Studies in animal models have long shown that non-competitive NMDA receptor antagonists, including PCP, ketamine and MDMA cause neurodegeneration.
MDMA-induced neurodegeneration is selective to serotonergic neurons and there is compelling evidence that recreational usage of the drug also damages serotonergic neurons in humans
What are the 2 types of Hallucinogen/MDMA treatment?
-Classical hallucinogen/MDMA-assisted psychotherapy
-Ketamine for severe treatment-resistant depression
What is Ketamine-induced ulcerative cystitis regarding adverse effects of dissociative anaesthetics and MDMA?
Thickening of bladder wall and low bladder capacity, kidney dysfunction has also been reported in chronic ketamine users.
What is Classical hallucinogen assisted therapy?
(Treatment)
Drug is used on one or a few occasions during psychotherapy sessions to overcome obstacles to facilitate a therapeutic experience.
What does research suggest about classical hallucinogen assisted therapy?
On-going research suggests may be helpful for severe depression and cancer anxiety but limitations regarding small samples and no placebo.
- MDMA toxicity for serotonergic neurons is of concern, although therapeutic effects of MDMA reported at substantially lower doses than those that have been shown to cause neurotoxicity
How is Ketamine used for severe treatment-resistant depression?
First clinical study in 2000 reported rapid anti-depressant effect of ketamine.
-Well-controlled clinical trials support antidepressant effect of ketamine, although not all patients respond, the duration of antidepressant effect is variable, and not all patient groups may be suitable eg psychosis
How is Ketamine used in current times to treat depression?
In 2019, nasal spray containing Esketamine (S(+)-ketamine) was approved for treatment-resistant depression in US and Europe, including UK, but NICE has not approved it for NHS funding
