What sort of roles have psychotropic plant drugs played in most cultures?
Religious practices, magic rituals and healing.
What are the best known hallucinogens in Europe?
Opium, hashish and ‘magic mushrooms’.
What do hallucinogens alter?
Sensory perception, awareness and thoughts.
What are some other terms for hallucinogens?
What drugs are classed as hallucinogens?
PCP, LSD, Psilocybin, MDMA and Mescaline.
What chemical class does mescaline belong to?
What chemical class does psilocybin belong to?
What chemical class does LSD belong to?
What hallucinogen is an amphetamine derivative?
What is the difference between dissociative anaesthetics and hallucinogenics?
They both produce hallucinogenic effects, but hallucinogens do not produce anaesthesia at high doses.
What plants is mescaline present in?
Cacti - San Pedro (Peru) and Peyote.
What is the proper name for ‘magic mushrooms’?
How was LSD discovered?
It is a synthetic drug related to compounds found in ergot fungus, which has been responsible for many cases of bread poisoning throughout history. In the 1940s Hofman discovered its hallucinogenic properties.
Who recommended the use of LSD in the 1960s?
Dr Timothy Leary - hippie culture.
When was recreational use of LSD banned?
Although hallucinogens vary in potency, they are all taken orally and effects, which begin 30-90 minutes following ingestion, last for around…
6-12 hours, a little less for Psilocybin-containing mushrooms.
What kind of structure do most hallucinogens share?
A serotonin-like or catecholamine-like structure.
What is the name for serotonin-like hallucinogens?
Which hallucinogens are indoleamine?
LSD and psilocybin.
What do Indoleamine hallucinogens do?
They are serotonin agonists.
Which hallucinogen is catecholamine-like (a phenethylamine hallucinogen)?
Mescaline - similar to noradrenaline and adrenaline.
What do hallucinogens do to affect serotoninergic pathways?
They act in the locus coeruleus (LC) and cerebral cortex via 5HT receptors - mescaline is a partial agonist of 5HT2 receptors and LSD agonises 5HT1, 2, 5, 6 and 7.
What did Appel et al (2004) find?
That rats much prefer LSD to saline in a drug discrimination task - they like LSD.
If then pretreated with serotonin antagonists (removes effects), LSD lever responses decreased dramatically.
What are the three 5-HT2A receptor antagonists that are successful (according to Vollenwieder et al, 1998) in blocking psilocybin-induced visual illusions and hallucinations?
What evidence is there that serotonin is involved in anxiety?
Genetic deletion of the 5-HT1A receptor increases anxiety-like behaviour.
What does the LC (main noradrenaline containing cell body in the brain) play a role in?
What are PCP and ketamine?
What effects do PCP and ketamine produce in low doses?
Signs of intoxication - staggering gait, slurred speech and catatonia at high doses.
What do PCP and ketamine do on a neural level?
They’re NDMA (glutamate) antagonists.
What is glutamate and how is it synthesised?
The major excitatory neurotransmitter, synthesised from glutamine in astrocytes.
Which neural pathways use glutamate?
Cortical association, cortico-thalamic, cortico-spinal, basal ganglia, hippocampal and cerebellar.
What are the three subtypes of glutamate receptor?
- AMPA and Kainate
What did Carlezon and Wise (1996) find?
Rats self-administer PCP to the nucleus accumbens, a part of the dopamine system involved in reinforcement.
What did Newcomer et al (1998) find?
That ketamine administration produces a dose-dependent increase in psychotic-like symptoms.
How are hallucinogenics used in psychiatric research?
There are common experiences between hallucinogen-induced states and schizophrenia, so they’re used to model psychoses.
Why is MDMA classed as a hallucinogen even though it’s an amphetamine analogue?
Because it changes perceptual awareness.
What does MDMA cause?
Feelings of euphoria, tingling, and a sense of increased sociability.
What does MDMA do to neurotransmitters?
Enhances the release of dopamine and serotonin.
About what percentage of university students have used MDMA?
What does MDMA stand for?
What did Liechti and Vollenweider (2001) find about the mechanism of MDMA?
(Used serotonin and dopamine receptor antagonists)
Serotonin = psychological effect
Dopamine = stimulant effects.
What does Ecstasy do to body temperature?
Induces changes in homeostatic control of body temperature due to altered hypothalamic function. Malberg and Seiden (1998) showed an increase in rats’ temperature when given MDMA, as also reported by around 90% of users.
There have been claims that ecstasy is less dangerous than…?
Is MDMA toxic according to biochemical and histological methods?
Yes, highly - selective neurotoxicity for the serotonin system, causes loss of fine axon endings that arise from the dorsal raphe nucleus.
What did McCann (1994) show as an effect of long term MDMA use?
Lower CSF 5-HIAA (metabolate of 5-HT)
What is serotonin syndrome caused by?
Gillman (1999) - drug-induced excess of intrasynaptic 5-HT.
What are the symptoms of serotonin syndrome?
Behavioural hyperactivity, agitation, mental confusion, hyperreflexia, tachycardia, shivering, clonus, termors.
What did Parrott (2002) note about clubbers?
They show many signs of serotonin syndrome.
What are ‘mid-week blues’?
2 days of increased depression after using MDMA - back to normal by day 7. Symptoms include energy loss and irritability.
What is a key factor in the neurotoxicity of MDMA?
Temperature - higher = greater neurotoxicity.
What is recovery like for long-term neurotoxic damage from MDMA?
Takes several months for rats, primates only ever partially recover (Ricaurte, 2000).
What does long-term MDMA use cause?
Loss of serotonin markers (5-HT, 5-HIAA) and 5-HT uptake sites (Ricaurte, 1985; Schmidt, 1986) - animal studies.
In humans, (McCann, 1998; Semple, 1999), reduced density of 5-HT transporter sites.
Is there a gender effect in the neurotoxicity of MDMA?
Yes, females more affected.
Does MDMA induce cognitive deficits?
+ Renemann (2000) - impairment in verbal learning.
+ Fox et al (2001) - lower spatial working memory.
What brain areas are most affected by Ecstasy?
Neocortex, hypothalamus, basal ganglia, amygdala and hippocampus.
What have case studies suggested might be the psychiatric consequences of MDMA use?
Major depression, panic disorder, aggressiveness, phobic anxiety, eating disorder, schizophrenia.
What did Schifano find to be the long term psychiatric effects of MDMA?
Higher depression, psychotic disorder, cognitive impairment, bulimia, impulse control and panic disorder. However, clinic attendes = not a representative sample.
What did Mechan, Moran et al (2002) find about the effect of MDMA on plus maze anxiety in rats?
What is the link between MDMA and dopamine?
Early studies suggested that dopamine release was increased, but Sabol and Seiden (1998) found that levels were decreased.
Mice show lowered striatal dopamine concentration, which is a long-term effect in mice but not rats.
What did Camarero et al (2002) find?
That MDMA reduces dopamine concentration (mice).
What did Gerra et al (2002) find about the effect of MDMA on dopamine in humans?
What did McCann et al (2008) find?
MDMA users had reductions in serotonin binding in multiple regions (correlated with memory function) but no lasting reductions in striatal dopamine binding.