CANNABIS II & CAFFEINE

C81ADD – The Psychology of Addiction

Dr. Mark Haselgrove

Overview of the lecture

(1) Cannabis Abuse, and chronic exposure effectsTolerance & DependenceAdverse behavioural and health effects

(2) Clinical applications of CannabisAnalgesiaAnti-emetic

(3) CaffeineBackground & PharmacologyBehavioural effectsTolerance & Dependence

Tolerance & Dependence

Brooks et al (1999)Longitudinal study of 776 ss fromNew York state.

Marijuana: A gateway to harder drugs….?

Age of initiation…

Most widely used illicit drug in UKand US (4.6 %, 14 Million in US)

- Difficult to asses, perhaps some users are more disposed to try harder drugs

Progression from initial to regular user…

Gruber & Pope (2002) Risk factors: Family disturbances, drug use by family/peers, School performance, age of onset

Tolerance & Dependence

With repeat use, does tolerance develop?

Mixed result in human studies:

(1) Compton et al. (1990) –

Tolerance observed following repeated administration of marijuana or pure THC.

(2) Kirk & de Wit (1999), Lindgren et al (1981) –

Same “high” in light/infrequent users relative to heavy/frequent users

Tolerance & Dependence

With repeat use, does tolerance develop?

Animal studies more consistent

Breivogel et al (1999): rats

Daily injections of THC (10 mg/kg)over 3 weeks

Progressive reduction in:

- CB1 receptor density- Cannabis agonist receptor activity.

- Some brain areas totally desensitized in 3 weeks.

Tolerance & Dependence

Dependence: (1) Difficulty stopping taking Cannabis

(2) Craving for cannabis(3) Withdrawal symptoms

A number of studies report that abstinence triggers:

- irritability, anxiety, depression, sleep disturbance, aggressiveness,- decreased appetite (e.g. Budney et al., 2003; Kouri et al.,1999)

Resemble nicotine withdrawalsymptoms

Worst in first 2 weeks – can for lastover a month

Tolerance & Dependence

Animal Studies:

- Early studies found no effect of drug withdrawal.- But THC has a long half life. Thus still present in system…

Precipitated withdrawal (e.g. Aceto et al., 1996):

Rats given twice daily THC injections Then given SR 141716 (CB1 receptor antagonist)

Rats displayed: symptons of hyperactivity (shaking, face rubbing, scratching)

Possibly a consequence of rats being stressed:

de Fonseca (1997) - ↑ Corticotrophin–releasing hormone (CRH) in precipitated withdrawal rats

Tolerance & Dependence

Treatment

Cognitive- behavioural therapy

Participants rewarded with vouchers forproviding cannabis- free urine samples

Significant relapse though: Moore & Budney (2003)

Haney et al., 2004: Withdrawal symptoms may be eased by oral consumption of THC

Useful in the short-term, difficult to achieve long-term abstinence.

Behavioural and health effects

(1) Psychological effects

Lynsky & Hall (2000) – chronic cannabis use → education performance

Greater cannabis use: More negative attitudes about schoolPoorer gradesIncreased absenteeism

Is this just a correlation or causation?

Lynsky & Hall (2000) - Amotivational syndrome: apathy; aimlessness; lack of productivity, long term planning and motivation

Behavioural and health effects

(1) Psychological effects

Solowij et al. (2002) – Cognitive deficits in long term users

Standardised tests of learning, memory and attention: long-term users deficient 1 and 7 days after exposure

Pope et al. (2001) – no difference between heavy users and controls after 28 days

Cognitive deficits linked to recent use – reversible over time.

Fergusson et al., (2003) Regular cannabis use early in life predicts poor school performance and drop-out rates

Matter for debate – Hot topic…

Behavioural and health effects

(2) Health effects

First, the good news…

No one reported to have died from Cannabis overdose

BUT,

(1) Higher concentrations of carcinogens in cannabis smoke than tobacco More tar and carbon monoxide/ joint than a cigarette

(2) Cannabinoids affect the immune system:Cabreal & Pettit (1998): THC suppresses immune function, increase risk of viral

and bacterial infection

(3) Cannabinoids affects reproductive function:Smoking in women suppresses luteinizing hormone release (but can be tolerated)Smith & Asch (1987) - ↓ sperm count in men (but only in heavy users)

Clinical applications

- Can be tracked back hundreds/thousands of years- Late C19 and early C20: crude extracts used in US and European treatments

Identification of THC → manufacture of synthetic compounds

DronabinolNabilone

Antiemetic for chemotherapy patientsAppetite stimulant on AIDS patients

Anecdotal evidence/limited clinical studies:

Cannabis also used for treatment of chronic pain: Multiple sclerosisSpinal cord injuryGlaucoma

Limited widespread use (especially in US) – (1) Side effects (2) Joints more effective than synthetics

BUT, HU-211, a cannabinoid that doesn’t activate CB1 receptors – no side effects Undergoing clinical trials

Caffeine – Background & Pharmacology

- Major source of caffeine = Coffee and Tea

- 80 - 90% of people regular drink.

- Average (adult) daily intake = 200 - 400 mg

- Consumption in children through chocolate & soft drinks

Caffeine – Background & Pharmacology

- Caffeine absorbed through the gastrointestinal tract (in about 30- 60 min)

- Plasma half life of around 4 hours, but usually topped up

People have a rising concentration in blood plasma throughout day

- Caffeine converted to metabolites by the liver

- 95% excreted in urine, 2 - 5% in faeces, rest through saliva

Behavioural Effects

Caffeine has a biphasic effect: Low dose- Stimulant, ↑ locomotor activityHigh dose – Reversed, ↓activity

More than just an arouser:

Smith et al., (1999)

Low- intermediate doses = variety of positive subjective effect

- SS instructed to abstain from coffee, tea etc- Beverage containing 40 mg caffeine

Could these positive effects be analleviation of withdrawal symptoms?

Rogers & Dernoncourt (1998)

Behavioural Effects

Tolerance & Dependence

Griffiths & Mumford (1995)Tolerance to subjective effects of caffeine

e.g. heavy drinkers can consume coffee before bed.

Abstinence → Withdrawal symptoms

Griffiths et al. (1990):

Withdrawal in (at least)100mg/day drinkers(1 cup a day)

Health effects (Chronic consumption): (1) ↑ blood pressure (2) ↑ coronary heart

disease (3) ↓ infant birth weight

Reading

Email: Mark.Haselgrove@nottingham.ac.uk

Meyer, J. S., & Quenzer, L. F. (2005). Psychopharmacology: Drugs,the brain and behavior. Sinauer. Chapter 13 & 12