SUHRT: Novel addiction therapy approaches (L2)

Harm caused by psychostimulants

• Psychosis

• Cardiac arrthmias

• Social harm

Physical withdrawal? No

Psychological withdrawal? Dysphoria and Stress

Psychological dependence? Yes

Harm caused by opiates

• overdose due to tolerance

• infectious diseases

• social harm

Physical withdrawal? Yes

Psychological withdrawal? Dysphoria and Stress

Psychological dependence? YES

Harm caused by alcohol

• Heart and liver  disease

• Cancer

• Neurological damage

• Malnutrition

• Social harm (violence)

Physical withdrawal? Yes

Psychological withdrawal? Dysphoria and Stress

Psychological dependence? YES

Harm caused by nicotine

• cancer

• heart disease

Physical withdrawal? Yes

Psychological withdrawal? Dysphoria and Stress

Psychological dependence? Yes

Tolerance

continued use of a drug requires increased dose for equivalent effect

How does alcohol enhance the risk of opiate overdose?

It reverses the densensitization at the m-opioid receptor (reverses the tolerance) so the higher dose taken has an overdose effect

Gabapentin does the same thing!!

Withdrawal

physiological effects when you stop taking the drug present in alcohol, opiates and nicotine

How to treat alcohol withdrawal?

benzodiazepines - chlordiazepoxide

anti-epileptics

antipsychotics

How to treat opiate withdrawal?

clonidine

benzo

sedation

replacement therapy e.g. methadone

How to treat nicotine withdrawal?

replacement therapy

• nicotine gum

• patches

Current drug treatments for withdrawal

replacement/substitution therapy

aversion therapy

antagonists/antibodies

Varenicline

nicotonic receptor partial agonists - works via the same pathway as nicotine replacement therapy

Disulfiram

used for alcoholics - aversion therapy

usually:

ethanol → acetaldehyde → acetic acid

with disulfiram:

the acetaldehyde → acetic acid pathway is blocked

build up of acetaldehyde which makes you feel horrible if you continue to drink

Psychological dependence

• Difficulty stopping drug use or limiting drug intake

• Extremely high motivation to take the drugs, with activities focussed on its procurement and consumption

• Substance use is continued despite its harmful consequences

• Only a small proportion of people who use drugs experience addiction

• High propensity to relapse after cessation of use

3 major stimuli for relapse

• small dose of drug

• dtress

• being presented with a cue associated with drug-taking

Main goal of substance use disorder treatment

to prevent relapse

Antagonists for stress hormone

antalarmin - CRH-1 receptor antagonist

mifepristone - glucocorticoid receptor antagonist

still in research

Dynorphin

endogenous agonists at k receptors

activates κ receptors (Gi/o) to suppress dopamine neurons directly

dynorphin is linked to:

• Dysphoria (feeling low/unpleasant)

• Stress and negative emotional states

• Anti-reward signalling