Definition of craving Although drug craving has been defined in numerous ways, it has generally been regarded as a desire to use a drug. It is a combination of thoughts and feelings. There is a powerful physiological components to craving that makes it a very powerful event and very difficult to resist. Craving is sometimes defined as a "subjectively experienced" desire or urge to approach and consume a particular substance
Brain Networks Associated With CravingDrugs of abuse activates the brain’s “reward circuit.”Neurons located in the nucleus accumbens extend to both the amygdala and the frontal cortex areas. The amygdala, which is highly connected to brain regions that control emotions (i.e., the limbic system), plays a role in the modulation of stress and mood. The frontal cortex areas integrate incoming sensory information, such as sights, smells, and sounds.
• Integration of sensory Prefrontal information cortex • reward memory is thought to be located Neucleus • plays a role in theaccumbence amygdala modulation of stress and emotions • which plays a role in basal repetitive thought and ganglia behavior patterns
Neurons located in the amygdala also send information to the DLPC and the basal ganglia. The DLPC sends information back to the basal ganglia (a connection that may play a role in obsessive-compulsive behaviors) and to the nucleus accumbens. Feedback from the DLPC to the nucleus accumbens may sensitize the latter to further drug exposure.
Neuroscientists discovered drugs also alter connections in brain circuits that govern learning and memory, causing the formation of strong associations between the drug’s pleasurable sensation and the circumstances under which it was taken. Drugs also disrupt brain circuits involved in impulse control in the prefrontal cortex, making it more difficult for addicts to resist taking drugs. Conversely, research suggests existing deficiencies in prefrontal function increase the risk of drug addiction. This finding may help explain why adolescents are more susceptible to addiction — the prefrontal cortex does not become fully developed until people reach their mid-20s.
Stage I: Set-up behaviors:Including: Physical factors, Psychological factors & Social factors.Stage II: Trigger Events for Craving: Thought Triggers. Feeling Triggers. Behavioral Triggers. Situational Triggers.Stage III: The Craving Cycle:Gorski (2001) proposed the craving cycle as a series of self reinforcing thoughts and behaviors that continue to activate and intensify the craving response.This cycle is marked by obsession, compulsion, physical craving, and drug- seeking behavior.
Opioid system: The mu subtype appears to be a key in opiate addiction: for mice lacking this receptor, morphine is no longer rewarding or reinforcing. Neuroimaging studies suggest that alterations in mu receptor level may be fundamental to addiction. Increased receptor levels in the anterior cingulate was found in recently abstinent humans addicted to cocaine or opiates; which may reflect elevated mu opiate receptor levels or decreased endogenous opioid levels leading to craving. Roles for kappa and delta opiate receptors in addiction are also evident. Unlike mu receptors, kappa receptor stimulation reduces dopamine function in the NAcc. This may possibly result in dysphoria. In animal models, delta antagonists can reduce self-administration of alcohol, suggesting that this receptor also plays a key role in reinforcement.
GABA SystemsGamma-aminobutyric acid (GABA) is the primary inhibitoryneurotransmitter in the brain.Sedative-hypnotic drugs including alcohol, benzodiazepines(e.g., Valium®), and barbiturates have long been hypothesizedto modulate receptors in GABA systems.Supporting this concept, experimental drugs that decrease thefunction of GABA receptors reduce alcohol consumption by rats.Microinjections of GABA antagonists into various rat brain.Regions suggest that an important brain area for alcohol- GABAinteractions is the central nucleus of the amygdala, a structurethat communicates with the basal forebrain structures and isassociated with emotion and stress.
NALTREXONE (ReVia®; Vivitrol®) opioid antagonist medication that binds to opioid receptors but does not activate them. useful for highly motivated recently detoxified patients who want total abstinence . How it works: Naltrexone blocks the part of your brain that feels pleasure when taking narcotics. Because it blocks the opioid receptors it prevents the body from responding to opiates It can be taken by mouth once daily or every other day, has minimal side effects and is not addicting. A favorable treatment outcome requires some form of psychotherapy, careful monitoring of medication compliance and effective behavioral interventions. Side effects: Nausea, vomiting, diarrhea, constipation, headache, dizziness.
METHADONE (Dolophine®; MethadoneDiskets®) Methadone blocks the receptors in the brain that are affected by opiates such as heroin, enabling users to gradually detoxify from opiates without experiencing painful withdrawal symptoms. Methadone occupies the receptors in the brain that opiates use, blocking the high feeling that opiates provide and making the user feel more stable. This reduces the drug cravings and withdrawal symptoms that often lead to relapse. Because Methadone’s effects last between 24 and 36 hours, most patients can be maintained on one daily dose. Side effects: Drowsiness, weakness, nausea, constipation, headache, loss of appetite.
BUPRENORPHINE (Buprenex®; Subutex®,Suboxone) Buprenorphine hydrochloride is a semi-synthetic partial µ- opioid receptor agonist Approved for treatment of pain and as a maintenance treatment for opioid dependence . Several studies have shown that a dose of 8 mg of Buprenorphine daily, administered sublingually is roughly equivalent of a 60 mg daily dose of methadone. SUBOXONE :Buprenorphine and Naloxone Because Naloxone has poor oral and sublingual bio- availability, it does not interfere with the effects of sublingually administered Buprenorphine. This combined preparation appears to be as effective as Buprenorphine alone and is less likely to be abused by patients
Baclofen a GABA B receptor agonist that inhibits the release of several neurotransmitters, including dopamine, noradrenaline, 5HT, and glutamate . Baclofen, through inhibition of somatodendritic dopamine release, prevents development of cocaine-induced behavioral sensitization and abolishes the motor-stimulant actions of cocaine. Baclofen was recently shown to attenuate the reinforcing effects of cocaine in rats. Other studies suggest that baclofen may be a fast acting treatment for the affective state that occurs during cocaine abstinence and, hence, may promote greater engagement in psychosocial treatment.
Antalarmin Corticotropin releasing hormone antagonist inhibit CRF-stimulation of cAMP or CRF-stimulated ACTH release from cultured rat anterior pituitary cells. sauvagine binding to CRF1 receptors in brain sections demonstrating their ability to cross the blood-brain-barrier. In in vivo studies, peripheral administration of these compounds attenuate stress-induced elevations in plasma ACTH levels in rats demonstrating that CRF1 receptors can be blocked in the periphery
In several experiments on rats; Antalarmin prevent dose escalation with prolonged use, suggesting that it might stabilise cocaine use and prevent it increasing over time, although without consistently reducing it. Antalarmin also showed positive effects in reducing withdrawal syndrome from chronic opioid use, and significantly reduced self-administration of ethanol in ethanol-addicted rodents.