Psychoactive Drugs in Neuropsychiatry Flashcards
What are the two main components of Cannabis?
▪️Cannabidiol (CBD)
▪️Tetrahydrocannabinol (THC)
Which component of cannabis is the psychoactive part?
THC
What is the endogenous ligands of the endocannabinoid system and where does it come from?
▪️Anandamide
▪️Released by postsynaptic neuron in response to increased Ca2+ or activation of specific receptors
What are the main receptors of the endocannabinoid system?
CB1 and CB2
How does cannabis act on the endocannabinoid system?
Binds to CB1 receptor much stronger than endogenous endocannabinoids such as Anandamide
Where does cannabis have it’s greatest effects?
▪️Mostly grey area regions (e.g. cortex)
▪️Midbrain (explains its benefits in pain management?)
Can cannabis be prescribed medicinally in the UK?
Yes! But not done often
What two cannabis-based medications have licensed indications in the UK?
▪️Sativex (for spasticity in MS)
▪️Nabilone (THC for chemo-induced nausea and vomiting)
▪️Also a form for paediatric epilepsy syndromes
(All the rest are prescribed off-license!)
What is Sativex and how is it usually prescribed?
▪️Oromucosal spray that’s 1:1 THC:CBD
▪️For spasticity in MS
(can only be prescribed by experts!)
How might CBD be used for Alzheimer’s disease in the future?
▪️Anxiety
▪️Agitation
What conditions are currently being research for cannabis-based interventions?
▪️Behavioural symptoms of AD
▪️Chronic neuropathic pain
What is the main concern for the use of cannabis based products in neuropsychiatry?
Risk of psychosis
Which component of cannabis is associated with increased psychosis risk?
THC
(unclear how protective CBD really is)
How does psychosis risk differ between US states that have legalised cannabis compared to those which haven’t?
No increased risk of psychosis BUT trends towards significance
What are stimulants?
Drugs that increase activity in the CNS such as amphetamines and amphetamine-related compounds
E.g. Methylphenidate, modafinil
What system do stimulants typically work on in the brain?
Dopamine transmission system
How does amphetamine typically work in the brain?
▪️Blocks reuptake of dopamine from synaptic cleft (also methylphenidate)
▪️Directly stimulates dopamine production
▪️Reverses dopamine uptake via the dopamine transporter
Why might amphetamines be related to higher rates of psychosis?
Action on the dopamine system leads to increased dopamine
What are the main stimulants used in neuropsychiatry?
▪️Methylphenidate
▪️Dexamfetamine
▪️Lisdexamfetamine
▪️Modafinil
▪️Atomoxetine
What are the main side effects of stimulants used for ADHD?
▪️Growth restriction
▪️Cardiac complications (increased HR, BP)
▪️Insomnia
What are the main uses of methylphenidate in neuropsychiatry?
ADHD
What other conditions may possibly be helped by methylphenidate?
▪️Apathy in AD and depression
▪️Cognitive function in TBI
What is modafinil currently licenced for in the UK?
Narcolepsy and other sleep disorders associated with excessive daytime sleepiness
What other conditions may possibly be helped by modafinil?
▪️Catalepsy in narcolepsy
▪️Fatigue in TBI and chronic fatigue
What type of drug is MDMA?
A stimulant
(3,4-methylenedioxy-methamphetamine)
What brain systems does MDMA act on?
Primarily serotonergic system but can act on the dopamine system too
How does MDMA work in the brain?
Encourages major serotonin release into the synaptic cleft through a range of actions (e.g. prevents 5-HT storage, switches direction of SERT to experort instead of import etc)
What are the main effects of MDMA?
▪️Wakefulness
▪️Anti-tiredness
▪️Pro-social
▪️Increased empathy
What is the main potential use for MDMA in neuropsychiatry?
Severe PTSD
How is MDMA proposed to aid treatment of severe PTSD?
▪️MDMA-assisted therapy
▪️Improves ability to open up and talk about trauma
What is the main effect of ketamine in the brain?
▪️Acts on NMDA receptors of GABA neurons
▪️Prevents them from inhibiting glutamate release
▪️Produces acute dissociative effects
What are currently the three main forms of ketamine used medicinally?
▪️Nasal spray esketamine (not in UK)
▪️Tablet
▪️IV ketamine
What is ketamine most commonly used for medicinally?
A sedative
What are the main potential use for ketamine in neuropsychiatry?
▪️Treatment-resistant depression - acutely improves mood and possibly suicidality
▪️FND?
What are the main issues with ketamine trials in neuropsychiatry?
▪️Difficult to blind
▪️Quite bitter
What is therapeutic sedation?
Using drugs to induce a dissociatove/hypnotic state to facilitate therapy
For what disorder might therapeutic sedation show the most promise?
FND
E.g. induced by anaesthetic before PT shown to help people with motor related FND (Stone, 2013)
Historically, what conditions have shown the best response to psychedelics?
▪️Depression
▪️Anxiety
▪️Alcohol/Substance misuse
▪️PTSD?
What psychedelic is most commonly used in research?
Psilocybin
Why might psychedelics have important cross-diagnostic potential?
▪️Target common underlying mechanisms (e.g. negative habits, biases, ruminations)
▪️Disrupt these as oppose to the conditions themselves?
What is the main issue with psychedelic research?
Interplay between placebo and expectancy:
▪️Hard to truly blind
▪️Psychedelics modulate expectancy, making people more suggestible which increases placebo effects
▪️Placebo group gets negative expectancy effect
What is the predictive processing model in FND?
▪️Brain makes predictions based on experience
▪️These are mainly accurate
▪️Prediction is stronger than sensory input so we experience something in the middle
▪️In FND, expectation is greater so experience symptoms despite sensation
How might psychedelics improve FND symptoms based on the predictive processing model?
▪️Disrupt predictive processes
▪️Reduction of influence of top-down predictions
▪️More sensory mediated experience
What brain regions are most commonly implicated in FND studies and how might psychedelics effect this?
▪️Default mode network
▪️Psychedelics may reduce DMN connectivity
▪️Deconstraining effect = enhancing communication between new networks
▪️Reduces prediction errors?
How is LSD thought to help FND?
Modification of neural circuits associated with self-representation
What is the PsiFund?
A open-label fMRI study of oral psilocybin plus psychological support for FND
