Understanding Drug Addiction: Diagnosis, Neurobiological Mechanisms, and Treatment, Slides of Pharmacology

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MECHANIS

M OF

DRUG

DEPENDA

NCE

DRUGS OF

ABUSE

Dr. Amullya Pednekar Department of

INTRODUCTION

WHAT IS A DRUG?

Any chemical compound or substance intended to affect the structure or function of body of man or animal that may be administered to help diagnose, treat, cure, mitigate, or prevent disease.

DRUG ABUSE

Habitual use of drugs not needed for therapeutic purposes (e.g. such as solely to alter one's mood, affect, or state of consciousness) or to affect a body function unnecessarily

DSM-5 guidelines for the diagnosis of a Substance Use Disorder requires that the individual have significant impairment or distress from their pattern of drug use, and at least two of the symptoms listed below in a given year

1. Using more of a substance than planned, or using a substance for a longer interval than desired
2. Inability to cut down despite desire to do so
3. Spending substantial amount of the day obtaining, using, or recovering from substance use
4. Cravings or intense urges to use
5. Repeated usage causes or contributes to an inability to meet important social, or professional obligations

The DSM-5 includes specifiers for severity of a SUD: MILD: Individuals meeting 2 or 3 criteria MODERATE: Individuals meeting 4 or 5 criteria SEVERE: Individuals meeting 6 or more criteria

REWARD SYSTEM OF BRAIN

Addictive drugs are rewarding and reinforcing (i.e. are addictive) due to their effects on dopamine reward pathway

Most important transcription factors producing gene expression alterations are ∆Fos B, cAMP response element binding (CREB) protein and nuclear factor kappa B (NF-kB) ∆Fos B:  (^) Most important biomolecular mechanism in addiction because its overexpression in D1-type medium spiny neurons in nucleus accumbens (NAcc) is necessary and sufficient for many neural adaptations and behavioural effects (e.g., expression-dependent increases in drug self- administration and reward sensitization) seen in drug addiction  (^) ΔFosB expression in nucleus accumbens D1-type medium FosB expression in nucleus accumbens D1-type medium spiny neurons directly and positively regulates drug self- administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion

MECHANISM OF DEPENDENCE PSYCHOLOGICAL DEPENDENCE

• (^) 2 factors : CRF (Corticotropin releasing factor) CREB protein (cAMP response element binding protein)
• (^) In Nacc, CREB is activated by cAMP immediately after a high and triggers changes in gene expression that affects proteins such as DYNORPHIN ( peptides which reduce DA release in Nacc by temporarily inhibiting reward pathway)
• (^) A sustained activation of CREB thus forces a larger dose to be taken to reach the same effect
• (^) In addition users are left depressed and dissatisfied and unable to find pleasure in previously enjoyable activities leading to return to drug for another dose

• (^) In addition, stress mechanism plays role in dependence
• (^) CRF activates HPA axis & other stress systems in extended amygdala which influences dysregulated emotional state associated with psychological dependence
• (^) drug use CRF in cerebrospinal fluid
• (^) Rat models  use of CRF inhibitors & CRF receptor antagonist both decreased self administration of drug of study

CLASSIFICATION

**1)Alcohol

2. Tobacco
3. Narcotics:**  (^) Heroin  (^) Codeine  (^) Methadone  (^) Morphine  (^) Opium  (^) Oxycodone  **Hydromorphon e
4. Stimulants:**  (^) Amphetamines  (^) Cocaine  (^) Khat  (^) **Methylphenidate
5. Depressants:**  (^) Barbiturates  (^) Benzodiazepines  (^) GHB  (^) Methaquanone  (^) Chloral hydrate  (^) Meprobamate

6) Hallucinogens:  (^) LSD  (^) MDMA  (^) K2/spice  (^) psilocybin  (^) peyote  (^) DMT  (^) **Ayahuasca

7. Marijuana or cannabis
8. Dissociative agents:**  (^) PCP  (^) Ketamine  Dextromethorpha n  (^) **Salvia divinorum
9. Anabolic steroids
10. Inhalants**