lecture 5- psychedelic drugs Flashcards
what are the classic psychedelic drugs?
- LSD (lysergic acid diethylamide; made from lysergic acid found in rye ergot fungus)
- psilocybin (found in magic mushrooms)
- psychedelic= mind revealing, mind testing
- hallucinogen= causing hallucinations, psychedelics can cause halluncinations; more often, they cause distortions of perception
- psychotomimetic = ‘mimicking psychosis’
— they can trigger (new) or increase (existing) psychotic effects (hallucinations, delusions)
— these effects can persist long-term
(all share a similar chemical structure)
altered perception
e.g., increased vividness of colours; distortions of apparent size of objects; synaesthesia; illusions of movement;
hallucinations, ranging from simple geometric patterns to complex images of objects & people
what are the acute subjective effects?
- altered perception
- subjectively pleasant effects
- subjectively unpleasant effects
subjectively unpleasant effects
– incl. ‘loss of self’: ‘anxious ego
dissolution’ – frightening feelings of ‘depersonalization’ & ‘derealization’; ideas of reference & paranoia; fear, panic & dangerous behaviour
subjectively pleasant effects
– incl. ‘loss of self’: feelings of
‘boundlessness’, ‘undifferentiated unity’; altered sense of time & space; often described in mystical or religious terms
mechanism for psychedelic effect
- shared indole ring structure
suggests psychedelics effects involve serotonin (5-HT) receptors but..
- simply increasing 5-HT activity throughout the brain (e.g., with SSRI) doesn’t produce similar effects,
– and neither does simply reducing 5-HT activity (e.g., using ATD).
what is the selective effect on 5-HT receptors: ?
- at least 14 distinct sub-types of serotonin (5-HT)
- Psychedelic drugs are 5-HT agonists, but only for some 5-HT receptor types (& could be antagonists at others)
- 5-HT 2A receptors in prefrontal cortex & thalamus are main site of
agonistic action:
– PFC = high-level cognition, conceptual thinking, sense of self
– thalamus = sensory ‘relay station’, with inputs from sense organs & outputs to
sensory cortex - Disruption of these systems could be basis for ‘psychedelic’ experiences (disrupted sense of self, alterations in perception, synaesthesia).
neural correlates of the psychedelic state- (Carhart-Harris et al., 2012, PNAS 109, 2138-2143)
- Psilocybin (v. placebo) significantly decreased neural activity
in a number of cortical (e.g. PFC) & sub-cortical (e.g. thalamus)
brain areas. - Intensity of subjective experience correlated significantly with
observed reductions in neural activity.
imaging studies show that psychedelic drugs:
‒ reduce neural activity in brain areas involved in maintaining a sense of self (the ‘default mode network’);
‒ increase functional connectivity between brain areas that usually don’t communicate much.
- Again, these neurophysiological changes correlate with subjective intensity of experience.
Griffiths et al. (2006): Effects of a single dose of psilocybin
- Griffiths et al. (2006, Psychopharmacology 187, 268-283) – effects of single dose of psilocybin in selected healthy, religious/spiritual, volunteers.
- Used methylphenidate (stimulant; non-psychedelic) as “active placebo” in a double-blind, within-subjects design.
- Acute effects of psilocybin (v. methylphenidate): changes in perception (visual pseudo-hallucinations, synaesthesia) & cognition (sense of meaning, ideas of reference); highly labile mood (alternating between intense joy, sadness & anxiety)
- More participants reported mystical experiences and persisting positive effects following psilocybin than following methylphenidate
- BUT there were effects of methylphenidate too, suggesting
expectancy effects in both groups…
BUT there were effects of methylphenidate too, suggesting
expectancy effects in both groups…
- After seven hours, reports of a “complete” mystical experience:
– 61% following psilocybin
– 11% following methylphenidate - After two months, ratings of experience being “among top five
most spiritually significant experiences”:
– 38% following psilocybin
– 8% following methylphenidate - After two months, self-reported “moderate” increase in well-being / life satisfaction:
– 50% following psilocybin
– 17% following methylphenidate - 14-month follow-up (Griffiths et al., 2008) – persisting effects “of psilocybin” reported … but this was the case after both treatments.
- Stringent safety precautions (incl. screening of volunteers; clinician involvement before, during, after) to avoid/manage potentially
dangerous negative drug effects. Nevertheless:
- Stringent safety precautions (incl. screening of volunteers; clinician involvement before, during, after) to avoid/manage potentially
– 11/36 volunteers reported strong/extreme fear following psilocybin
(none following methylphenidate); two compared it to being in a
war.
– 6/36 experienced ideas of reference/ paranoid thinking following
psilocybin.
- Volunteers were not general population: highly educated (majority
post-grad); healthy & low risk; religious/spiritual, interest in effects
of drugs & extensive self-reflection opportunity. - “Blinding” to conditions may have been ineffective.
is there a place for psychedelics in therapy?
- Long & controversial history (N.B., LSD & psilocybin remain illegal in UK)
- There are (somewhat inconsistent) reports of possible positive effects for LSD- & psilocybin-assisted psychotherapy in treating:
– addictions (including alcohol & tobacco),
– obsessive-compulsive disorder, and
– depression & anxiety in patients with life-threatening or terminal illnesses - Currently very active area of research
psychedelic-assisted psychotherapy
- Current approach uses administration as part of a carefully monitored, on-going programme of psychotherapy –
– psychedelics are used to “facilitate & intensify ongoing therapeutic processes, but not to replace them” (Majić et al., 2015)
- Some studies have identified an “afterglow period” (possibly lasting for weeks) when effectiveness of psychotherapy is enhanced – the experience seems to challenge patient’s current world-view & increase openness to alternative perspectives suggested by therapist
possible distinct therapeutic mechanisms for SSRIs and psychedelics:
- ‘Cortical entropy’: complexity of interactions between brain areas usually ‘segregated’ from each other – its increase in psychedelic drug
states is hypothesised to be mechanism for reducing ‘rigid thinking
HAVNET TYPED TABLE YET GO TO SLIDES!!!!!!!!!
recently published clinical trials
- Carhart-Harris et al., NEJM, 2021 [Link]
– 25mg psilocybin and daily placebo versus 1mg psilocybin and daily escitalopram (SSRI). Both with psychological support.
– No sig. difference on primary outcome measure (change on self-report depression scale). Did both work or did neither work?
- Goodwin et al., NEJM, 2022 [Link]
– Three doses of psilocybin compared: 25mg, 10mg, 1mg, all with psychological
support.
– Sig. greater improvement on primary outcome measure (other-rated MADRS)
with 25mg versus 1mg, but not with 10mg versus 1mg.
– Adverse events noted.
- Both recommend larger and longer trials.
