Craving

Karen Drexler, M.D.

July 30, 2003

[Slide #1]

I. Overview (Slide #2)

A. What is craving?

B. Why is it so compelling?

C. How do we measure it?

D. What are the neural mechanisms that drive craving?

E. How can we treat it?

II. What is craving? (Slide #3)

A. First hand description:

One man with cocaine dependence describes it: “An intense craving for me is when my heart starts beating fast- actually, I get a little sweaty- and all I think about doing is just going to smoke. That’s it. Nothing else- everything that’s on my mind just kind of disappears. First you start thinking about it, then your body almost reproduces the feeling that you get from a high.” (1)

B. Key features of craving

1. An intense desire that compels drug-seeking behavior in dependent individuals.

a) Halikas- “Craving is to desire what panic is to anxiety” (2)

b) Not just a thought, physiological symptoms (heart racing, palms sweaty, etc)

2. Compels drug seeking in dependent individuals- common in dependent individuals, but not in occasional users. (3,4)

(Slide #4)

a) What do we mean by “dependence”?

b) DSM-IV defines psychoactive substance dependence as “ a cluster of cognitive, behavioral and physiological symptoms indicating that the individual continues substance use despite significant substance-related problems”. (5)

c) DSM-IV criteria for diagnosis- 3 or more of the following occurring within the same 12 month period of time

(1) Tolerance

(2) Withdrawal

(3) Substance taken in larger amounts that intended

(4) Persistent unsuccessful efforts to cut down or control substance use

(5) A great deal of time spent getting the substance, using it, being intoxicated and/or recovering from its effects

(6) Important activities given up or reduced in order to continue using the substance

(7) Continued use despite knowledge of a psychological or physical problem exacerbated by use of the substance

d) Understanding craving may help us to understand some of the more baffling features of this illness.

(1) Why do dependent individuals end up using more than they intend?

(2) Why is it difficult to cut down or control use?

(3) Why do individuals who have suffered multiple severe problems as a result of substance use relapse after a period of abstinence?

III. Why is craving so compelling? (Slide #6)

A. Triggers drug use in dependent individuals.

B. Craving correlates with drug use in dependent individuals.

1. Cocaine craving correlates with cocaine use in previous 30 days (6)

2. Cocaine craving is associated with cocaine use during aftercare- craving doubled during periods of cocaine use and cocaine use was 4 times higher in periods of craving (7) (Slide #7)

3. Alcohol craving correlates with other measures of alcohol dependence. (8)

C. Craving decreases with treatment

1. Cocaine and alcohol craving decrease over 28-days of inpatient rehabilitation (9,10)

2. Alcoholic patients taking naltrexone have less craving and fewer relapses. (11)

D. Craving can predict treatment outcome. In general, more recent, outpatient studies using multidimensional craving measures have found a significant relationship.

1. Persistence of cue-induced cocaine craving predicts relapse (12)

2. Alcohol craving at week 2 correlates with relapse in weeks 3 – 12. (13)

3. Alcohol craving during negative mood states predicts time to relapse (14)

IV. How do we measure craving? (Slide #8)

A. Multidimensional scales (Slide #9)

1. Correlate with treatment outcome. (15)

2. Measure multiple aspects:

a) intensity,

b) frequency,

c) physical and psychological components

3. Examples include:

a) Alcohol-

(1) The Yale-Brown Obsessive Compulsive Scale modified for heavy drinkers. (3) (16)

(2) The Obsessive Compulsive Drinking Scale for alcohol dependence. (17) (8)

(3) The Penn Alcohol Craving Scale (13)

b) Cocaine-

(1) The Minnesota Cocaine Craving Scale (2)

(2) Tiffany Cocaine Craving Questionnaire. (18)

c) Nicotine-

(1) Fagerstrom Tolerance Questionnaire (19)

(2) Fagerstrom Nicotine Dependence Questionnaire (20)

B. Single variable intensity scales (Slide #10)

1. Correlate with physiologic measures.

2. Examples include visual analogue or Likert scales:

V. What are the neural mechanisms that drive craving? (Slide #11)

A. Three mechanisms help explain why craving develops in psychoactive substance dependence. (21) (Slide #12)

1. Sensitization of motivation for drugs through the mesocorticolimbic dopamine pathway causes urges to use to become more intense even as tolerance develops to the pleasurable effects of drugs and alcohol. (22) (Slide #13)

a) Ventral tegmental area (VTA) →

b) Medial forebrain bundle (MFB) →

c) Nucleus accumbens (NAcc)

d) Prefrontal cortex (PFC).

2. Degradation of inhibitory control mediated by the prefrontal cortex causes urges to become more compelling and irresistable. (23) (24) (Slide #14)

3. Enhanced stimulus-reward learning involving the amygdala and the nucleus accumbens and medial prefrontal cortex causes urges to become more frequent as more conditioned stimuli become associated with substance use. (25) (26) (27) (28) (Slide #15)

VI. Neural correlates of craving in humans (Slide #16)

A. Confirm these hypotheses- raise others.

B. Two types of provocation paradigms

1. Substance-induced craving - cocaine dependence: (Slide #17)

a) Craving associated with initial use of a substance is thought to drive the loss of control- in DSM-IV “often using more than intended”.

b) From above hypotheses, one might expect that use of a stimulant might activate the mesolimbic dopamine pathway (increased desire) and deactivate the orbitofrontal cortex (decreased inhibition).

c) Stimulants (Cocaine and methylphenidate) used to induce craving: (29) (30) (31,32)

d) In fact, stimulant injection is primarily associated with activation of ventral striatum and interconnected structures involved in reward processing (mesolimbic pathway), but also areas involved in sensory processing (thalamus), conditioned learning (amygdala), and cognitive control (orbitofrontal cortex (OFC). (33) (34) (35)

(a) Ventral striatum/ Nucleus accumbens (N Acc) –Reward processing and prediction (29)