CHAPTER ONE

1.0 INTRODUCTION

1.1 DEFINITION OF PSYCHOACTIVE DRUGS

Psychoactive drugs are substances that, when taken in or administered into one's

system, affect mental processes, e.g. perception, consciousness, cognition or mood and

emotions. Psychoactive drugs belong to a broader category of psychoactive substances

that include also alcohol and nicotine (WHO, 2020).

Psychoactive drugs alter synaptic transmission by

modulating neurotransmitter amounts and availability or by affecting receptor activity.

In addition to their primary effects on mental processes – arousal, perception, mood,

cognition, consciousness – these drugs produce a variety of non-behavioral effects that

are often far more dangerous to health, and, in some instances, can be lethal.

(A. Dietrich, 2009)

1.2 BRIEF HISTORY OF PSYCHOACTIVE DRUGS

Psychoactive drug use can be traced back to prehistory. There is archaeological evidence

of the use of psychoactive substances, mostly plants, dating back at least 10,000 years

and historical evidence of cultural use over the past 5,000 years. (Merlin, M.D (2003).

Man’s ingenuity seems inexhaustible for discovering natural drugs which alter

consciousness. Almost every society, however primitive, has been able to find in nature

some bark, skin, leaf, vine or weed which contains a material which allows one

1
temporarily get out of one’s head. One can only speculate about the process whereby so

many different agents were discovered. Very likely such discoveries were accidental: A

hungry hunter or warrior would eat a strange plant or food, only to discover its unusual

powers on his mind. These empirical discoveries of mind-altering drugs occurred over

several millennia and in virtually all parts of the world. Despite the variety of different

agents discovered to have intoxicating properties, most societies limited these drugs to

relatively few uses. The predominantly use was for producing mystical experience, a

sense of communion with gods. Persons under the influence of these agents were

believed to have supernatural powers of healing and divination. (Leo E. Hollister, 1972).

1.3 ROUTES OF ADMINISTRATION

Psychoactive drugs are administered via oral ingestion as a tablet, capsule, powder,

liquid, and beverage; via injection by subcutaneous, intramuscular,

and intravenous route; via rectum by suppository and enema; and via inhalation

by smoking, vaporizing, and snorting. The efficiency of each method of administration

varies from drug to drug. (United States Food and Drug Administration, 2006-01-03).

The psychiatric drugs fluoxetine, quetiapine, and lorazepam are ingested orally

in tablet or capsule form. Alcohol and caffeine are ingested in beverage

form; nicotine and cannabis are smoked or vaporized; peyote and psilocybin

mushrooms are ingested in botanical form or dried; and crystalline drugs such

as cocaine and methamphetamine are usually inhaled or snorted.

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1.4 REASONS FOR PSYCHOACTIVE DRUG USE

Results from the most recent British Crime Survey show that some 50% of young people

between the ages of 16 and 24 years have used an illicit drug on at least one occasion in

their lives (lifetime prevalence) (Ramsay and Partridge, 1999).

Similarly, research with a focus on young people has sought to identify motives for illicit

drug use. There is evidence that for many young people, the decision to use a drug is

based on a rational appraisal process, rather than a passive reaction to the context in

which a substance is available. (Boys et al. 2000a)

Reported reasons vary from quite broad statements (e.g. to feel better) to more specific

functions for use (e.g. to increase self-confidence).

Given the diverse effects that different drugs have on the user, it might be proposed that

reasons for use will closely mirror these differences. Thus stimulant drugs (such as

amphetamines, ecstasy or cocaine) will be used for reasons relating to increased nervous

system arousal and drugs with sedative effects (such as alcohol or cannabis), with

nervous system depression.

In the medical world, psychoactive drugs are used on people to block physical pain and

other sensations. Most anesthetics induce unconsciousness, allowing the person to

undergo medical procedures like surgery, without the feelings of physical

pain or emotional trauma (e.g Ketamine, Propofol). Some others are used to manage

pain (e.g Codeine, Morphine) or mental disorders.

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1.5 CONCLUSION

Psychoactive drugs use dates back many years and reasons for its use are myriad. Its

spread can be explained by the potential of having multiple routes of administration for

psychoactive drugs easy to use and afford.

4
 CHAPTER TWO

2.0 CLASSES OF PSYCHOACTIVE DRUGS

Psychoactive drugs fall into different categories, depending on what effects the drug has

on a person. These include:

 Depressants: These drugs can calm the brain, causes sleepiness, and make a

person feel relaxed. However, they can also cause nightmares, anxiety, and

aggression. Alcohol is an example of a depressant.

 Stimulants: These include drugs such as cocaine and caffeine. Stimulants can

increase energy, alertness, and wakefulness.

 Opiates: These are pain-killing drugs that increase feelings of happiness or

euphoria and create a tranquilizing effect. They can lead to addiction if a person

misuses them, and they include drugs such as heroin.

 Hallucinogens: These drugs can cause a person to have hallucinations, which

means they may see or hear things that are not there. They can also cause a

person to perceive time differently, feel detached from their surroundings, or feel

deeply insightful. LSD is an example of a hallucinogen.

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2.1 DEPRESSANTS

Depressant substances reduce arousal and stimulation. They affect the central nervous

system, slowing down the messages between the brain and body. They can affect

concentration and coordination and slow down a person’s ability to respond to

unexpected situations. In small doses, they can cause a person to feel more relaxed and

less inhibited. (Brands B et al [cited 2021 May)

In larger doses they can cause drowsiness, vomiting, unconsciousness and death.
[Australian Government Department of Health. Types of Drugs - Drug catagories 2019 [12.01.2021].

Common street names for depressants include Barbs, Benzos, Downers, Georgia Home

Boy, GHB, Grievous Bodily Harm, Liquid X, Nerve Pills, Phennies, R2, Reds, Roofes,

Rophies, Tranks, and Yellows.

2.2 STIMULANTS

A stimulant is a drug that stimulates the body and mind activity. Some of the most

commonly used stimulants are caffeine, cocaine, amphetamines, and Ecstasy (MDMA,

methylenedioxyamphetamines). Out of the above listed caffeine is the most widely used

and has very mild side effects. Caffeine is found in coffee, teas, soda, and chocolate.

Caffeine is the most commonly used stimulant in the world, used for a combination of

dietary and recreational purposes as well as performance enhancement. Other legal

stimulants are generally used for performance enhancement but may also find utility for

specific symptoms depending on the drug. Illegal and/or prescription stimulants carry

6
medical purposes but are also heavily used for recreational reasons. (Cornelis MC. 2019 Feb
16;11(2)

The amphetamine class of drugs is used for medical and recreational purposes. They

carry a multitude of effects that include general and cognitive performance

enhancement along with euphoric effects. They also induce aphrodisiac effects in many

users. ADHD treatment commonly uses a combination of dextroamphetamine and

levoamphetamine, as well as pure dextroamphetamine and lisdexamfetamine.

Methamphetamine is a widely trafficked and illegal drug used for recreational purposes.

Athletes use many medications related to the amphetamine class of drugs for physical

performance enhancement. These drugs fall under bans by the world anti-doping

agency (WADA). (Heal DJ et al, 2013 Jun).

2.3 OPIATES

Opioids are a broad group of pain-relieving medicines that work with your brain cells.

Opioids can be made from the poppy plant — for example, morphine (Duramorph, MS

Contin, others). Or opioids can be made in a laboratory — for example, fentanyl (Actiq

and Fentora). Other opioids that may sound familiar include codeine, hydrocodone

(Vicodin), oxycodone (OxyContin, Roxybond, others). But there are many more.

Opioid medicines travel through the blood and attach to opioid receptors in brain cells.

This blocks pain messages and can boost feelings of pleasure. (Tyler S. 2018)

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2.4 HALLUCINOGENS

Hallucinogens fall into several different classes, as broadly defined by pharmacological

mechanism of action, and chemical structure. Although these classes do not share a

common primary mechanism of action, they do exhibit important similarities in their

ability to occasion temporary but profound alterations of consciousness, including acute

changes in somatic, perceptual, cognitive, and affective processes. Such effects likely

contribute to their recreational use. However, a growing body of evidence indicates that

these drugs may have other applications beyond their potential for abuse. A number of

naturally occurring hallucinogens have a long history of use as religious sacraments

dating back hundreds, and in some cases, thousands of years (El-Seedi et al., 2005; Guerra-

Doce, 2015; Li, 1973).

These include serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid

diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), often referred to

as classic hallucinogens or psychedelics; mixed serotonin and dopamine reuptake

inhibitors and releasers such as 3,4-methylenedioxy-methamphetamine (MDMA),

referred to as empathogens or entactogens, N-methyl-D-aspartate (NMDA) antagonists

such as ketamine and dextromethorphan (DXM), also known as dissociative anesthetics.

2.5 CONCLUSION

There are several different classification schemes for psychoactive substances –

according to legal, medical, or pharmacological criteria – but the most common

organization is based on their effect on behavior.

CHAPTER THREE

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3.0 METABOLISM OF PSYCHOACTIVE DRUGS

Metabolism involves the breakdown of psychoactive drugs, and this occurs primarily in

the liver. The liver produces enzymes (proteins that speed up a chemical reaction), and

these enzymes help catalyze a chemical reaction that breaks down psychoactive drugs.

Enzymes exist in “families,” and many psychoactive drugs are broken down by the same

family of enzymes, the Cytochrome P450 super family. Usually, there is not a unique

enzyme for each drug; rather, certain enzymes can break down a wide variety of drugs.

Drug metabolism occurs at a specific location in the body, resulting in a low

concentration of active metabolites in the systemic circulation. This phenomenon is

called first-pass metabolism because it limits drug bioavailability. First-pass metabolism

primarily occurs in the liver; however, metabolizing enzymes can be found throughout

the body. (Damasio A, (2013)

Most drugs are xenobiotics, ie, chemical substances not naturally produced by the body.

Xenobiotics undergo various body processes for detoxification, thus reducing their

toxicity and allowing them to be readily available for excretion. These processes allow

for the chemical modification of drugs into their metabolites and are known as drug

metabolism or metabolic biotransformation. (Wilde M, 2009)

3.1 PHASES OF METABOLISM

The kidneys are primarily responsible for the excretion of drugs from the body;

however, lipophilic drugs readily cross the cell membrane of the kidney tubules and are

reabsorbed into the blood. (Garza AZ et al, 2023). The metabolism of drugs can occur in

9
various reactions, categorized as phase I (modification), phase II (conjugation), and in

some instances, phase III (additional modification and excretion).

3.1.1 PHASE I METABOLISM

Phase I modifications alter the lipophilic drug chemical structure through oxidation,

reduction, hydrolysis, cyclization/decyclization, and either by removing hydrogen or

adding oxygen to more polar molecules. In some instances, this process changes an

inactive prodrug into a metabolically active drug. Oxidation typically results in

metabolites that still retain some of their pharmacological activity. For example, phase I

modification transforms the common anxiolytic drug diazepam into desmethyldiazepam

and then further into oxazepam. Both of those metabolites produce similar physiological

and psychological effects to diazepam itself. The cytochrome P450 system, also known

as microsomal mixed function oxidase, catalyzes most phase I reactions. (Azzam et al 2019

Jun)

3.1.2 PHASE II METABOLISM

In phase II modifications, a drug molecule couples with another molecule in a

conjugation reaction. Conjugation usually renders the compound pharmacologically

inert and water-soluble, allowing the compound to be easily excreted. Conjugation

mechanisms include methylation, acetylation, sulphation, glucuronidation, and glycine

or glutathione conjugation. These processes can occur in various locations, such as the

liver, kidney, lungs, intestines, and other organ systems. An example of phase II

metabolism is oxazepam, which conjugates with another molecule called

10
glucuronide. The drug becomes physiologically inactive and is excreted without further

chemical modification. (Boyland E, et al 2012.)

3.1.3 PHASE III METABOLISM

Phase III metabolism may also follow phase II metabolism, in which conjugates and

metabolites are excreted from the cells. A critical factor in drug metabolism is the

enzymatic catalysis of phase I and II processes. The type and concentration of liver

enzymes are crucial to the efficient metabolism of drugs. The most commonly used

enzymes for medical purposes are monoamine oxidase and cytochrome P450. These 2

enzymes are responsible for metabolizing dozens of biogenic and xenobiotic chemicals.

(Commandeur JN et al, 2015)

3.2 CONCLUSION

After "surviving" the processes of absorption and initial metabolism but before being

eliminated, drugs are distributed throughout the body until they reach their target. In

the case of psychoactive drugs, the main target is the brain

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 CHAPTER FOUR

4.0 EFFECTS OF PSYCHOACTIVE DRUGS

Every distinct brain area or neural circuit can be affected in some way by the action of

psychoactive drugs due to the integration process discussed above. For example, drugs

that increase endorphin activity (i.e. Opioids) in certain areas of the brain can trigger

changes in a major pain-inhibition pathway. Circuits involved with attention are

affected by drugs that enhance norepinephrine systems and can be effective treatments

for ADHD. Still other drugs, such as anti-anxiety medications (i.e. Xanax, Valium) are

GABA agonists and can enhance the action of GABA throughout the brain, including the

amygdala, which plays a significant role in fear and anxiety responses. (Rohsenow DJ et al,
1990 – 1991)

4.1 THE REWARD CIRCUIT

One of the most interesting and significant circuits that has been studied for its role in

drug taking and substance use disorder is the "reward circuit" or "pleasure pathway" of

the brain. This circuitry is technically called the mesolimbic circuitry and contains major

dopamine pathways in addition to other transmitters which play a role in the positive

feelings associated with both natural and drug rewards. (See Figure 4.1).

The nucleus accumbens definitely plays a central role in the reward circuit. Its

operation is based chiefly on two essential neurotransmitters: dopamine, which

promotes desire, and serotonin, whose effects include satiety and inhibition. Many

12
animal studies have shown that many psychoactive drugs and natural rewards increase

the production of dopamine in the nucleus accumbens, while reducing that of serotonin.

Figure 4.1: Mesolimbic, "Reward" Circuit and other Dopamine Pathways. These include

pathways from both the Substantia Nigra (SNc) and Ventral Tegmental Area (VTA) to

forebrain targets such as the Nucleus Accumbens and Prefrontal Cortex. From: Oscar Arias-

Carrión1, Maria Stamelou, Eric Murillo-Rodríguez, Manuel Menéndez-González and Ernst

Pöppel.Substantially modified by Seppi333, CC BY 2.0 , via Wikimedia Commons

13
But the nucleus accumbens does not work in isolation. It maintains close relations with

other areas involved in pleasure and reward. One area in particular is the ventral

tegmental area (VTA). Located in the midbrain, at the top of the brainstem, the VTA

is one of the most primitive parts of the brain. Neurons of the VTA synthesize dopamine

and then send it via their axons primarily to the nucleus accumbens. The VTA is also

influenced by endorphins whose receptors are targeted by opiate drugs such as heroin

and morphine.

Another structure involved in pleasure mechanisms is the prefrontal cortex, whose

role in planning and motivating action is well established. The prefrontal cortex is a

significant relay in the reward circuit and also is modulated by dopamine.

The second is the hippocampus, which preserves the agreeable memories associated

with drug taking or other non-drug behaviors and, by association, all of the details of the

environment in which these behaviors occur. The memory of these details may trigger

positive feelings and, in the case of drugs reawaken the desire to take the drug again

contributing to the possibility of relapse. (Damasio A, et al 2013)

4.2 MECHANISM OF ADDICTION

Substance and alcohol use disorders impose large health and economic burdens on

individuals, families, communities, and society. Neither prevention nor treatment

efforts are effective in all individuals. Results are often modest. Advances in

neuroscience and addiction research have helped to describe the neurobiological

changes that occur when a person transitions from recreational substance use to a

substance use disorder or addiction. Understanding both the drivers and consequences

14
of substance use in vulnerable populations, including those whose brains are still

maturing, has revealed behavioral and biological characteristics that can increase risks

of addiction. (Sagar et al, 2015)

Much progress in the neurobiology of addiction can be placed into a heuristic three‐

stage addiction cycle framework: binge/intoxication, withdrawal/negative affect, and

preoccupation/anticipation. This framework is supported by multiple neuroadaptations

in three corresponding domains: (1) increased incentive salience, (2) decreased brain

reward and increased stress, and (3) compromised executive function; and in three

major neurocircuits: basal ganglia, extended amygdala, and prefrontal cortex. The focus

in the neurobiology of addiction has changed with emphasis on the mechanisms of acute

reward in the binge/intoxication stage broadened to include neuroadaptations that are

consequent to drug exposure. These include mechanisms driving incentive salience,

compulsive habits, deficits in reward and recruitment of stress during the

withdrawal/negative affect stage, and modulation of executive function systems and

mnemonic systems (and being modulated by mnemonic processes) in the

preoccupation/anticipation stages of substance use disorders.

4.2.1 ROLE OF DOPAMINE IN ADDICTION

Addictive drugs are inherently rewarding. They highjack the brain's dopamine system to

increase dopamine levels in the nucleus accumbens, a key focal point for reward

neurocircuitry in the brain.6 While dopamine is critical for the rewarding effects of

drugs, its role in substance use disorders is still evolving.

15
Since the rate of dopamine increase plays a factor in whether a drug will produce a

rewarding effect, the different properties and effects of dopamine receptors in the brain

are likely to play significant roles. (Volkow et al, 2021)

The prefrontal cortex contains both dopamine D1 and D2 receptors. D2 receptors have

an approximately 10‐ to 100‐fold greater affinity for dopamine than D1 receptors and

are therefore activated at lower dopamine concentrations.

D1 receptors stimulate both reward, via pathways modulating the striatum and cortex,

and conditioning and memory mechanisms that involve the amygdala, medial

orbitofrontal cortex (OFC), and hippocampus. The conditioning/memory processes

critical to addiction allows individuals to automatically associate a stimulus with a

reward or punishment.

Normally, D2 receptors modulate the effects of D1 receptors via the striatal indirect

pathway;10 however, several studies have shown that addicted subjects have lower

expression of dopamine D2 receptors (Volkow et al, 2002)

4.2 TOLERANCE

Tolerance to a drug, including alcohol, was first described as a form of behavioral

plasticity and was defined as a decreased response to repeated drug exposures (Kalant

1998).

Tolerance to the effects of many drugs can occur with repeated exposure; that is, the

drug produces less of an effect over time, so more of the drug is needed to get the same

16
effect. This is particularly true for sedative drugs like alcohol or opiate-based painkillers

(e.g., fentanyl, codeine).

Tolerance can be described at different levels of biological complexity—molecular,

cellular, and behavioral—or by its temporal characteristics of how rapidly the alcohol

affects the organism.

4.2.1 Molecular Tolerance

Knowledge of molecular tolerance comes from dissecting adaptational processes

developed by individual molecules (e.g., ion channels) during exposure to a drug. The

current notion is that even complex behavioral traits can be traced to individual

molecules. All of alcohol’s complex effects on an organism start at the molecular level,

during interaction of an alcohol molecule with its molecular target(s).

4.2.2 Cellular Tolerance

Metabolic tolerance is one kind of tolerance and it takes place primarily in the liver.

Some drugs, such as alcohol cause enzyme induction – an increase in the enzymes

produced by the liver. For example, chronic drinking results in alcohol being broken

down more quickly, so the alcoholic needs to drink more to get the same effect – of

course, until so much alcohol is consumed that it damages the liver. (Damasio A,et al 2013)

17
4.2.3 Behavioural Tolerance

Currently, behavioral tolerance is divided into three categories: acute, rapid, and

chronic. Acute tolerance develops within a single drinking session, typically within

minutes, whereas chronic tolerance occurs after a longer time, usually following days of

continuous or intermittent alcohol exposure. Rapid tolerance shares many similarities

with chronic tolerance but develops faster, typically within 8 to 24 hours. (Crabbe et al.
1979)

4.3 DEPENDENCE

Drug dependence, is a biopsychological situation whereby an individual's functionality

is dependent on the necessitated re-consumption of a psychoactive substance because of

an adaptive state that has developed within the individual from psychoactive substance

consumption that results in the experience of withdrawal and that necessitates the re-

consumption of the drug. (Malenka RC et al, 2009)

The International Classification of Diseases classifies substance dependence as

a mental and behavioural disorder. ("The ICD-10 Classification of Mental and Behavioural

Disorders Clinical descriptions and diagnostic guidelines")

4.3.1 Psychological Dependence

The nucleus accumbens (NAcc) is one brain structure that has been implicated in

the psychological component of drug dependence. Two factors have been identified as

playing pivotal roles in psychological dependence: the neuropeptide "corticotropin-

18
releasing factor" (CRF) and the gene transcription factor "cAMP response element

binding protein" (CREB). (Malenka et al, 2009)

A sustained activation of CREB thus forces a larger dose to be taken to reach the same

effect. In addition, it leaves the user feeling generally depressed and dissatisfied, and

unable to find pleasure in previously enjoyable activities, often leading to a return to the

drug for another dose. (Giannini et al,1998.)

4.3.2 Physical Dependence

Upregulation of the cAMP signal transduction pathway in the locus

coeruleus by CREB has been implicated as the mechanism responsible for certain

aspects of opioid-induced physical dependence. (Nestler EJ (August 2016).

4.4 WITHDRAWAL

Withdrawal is the body's reaction to abstaining from a substance upon which a person

has developed a dependence syndrome. When dependence has developed, cessation of

substance-use produces an unpleasant state, which promotes continued drug use

through negative reinforcement; i.e., the drug is used to escape or avoid re-entering the

associated withdrawal state. The withdrawal state may include physical-somatic

symptoms (physical dependence), emotional-motivational symptoms (psychological

dependence), or both. Chemical and hormonal imbalances may arise if the substance is

not re-introduced. Psychological stress may also result if the substance is not re-

19
introduced. ("Are addictions classified as being a mental health disorder?". YouTube. 16 September
2020. Archived from the original on 11 November 2021. Retrieved 21 December 2020.)

Infants also experience substance withdrawal, known as neonatal abstinence

syndrome (NAS), which can have severe and life-threatening effects. Addiction to drugs

such as alcohol in expectant mothers not only causes NAS, but also an array of other

issues which can continually affect the infant throughout their lifetime. ("Supporting
mothers with opioid addiction is the best bet in fighting neonatal abstinence syndrome". sheknows.com.

10 May 2017. Archived from the original on 11 November 2017. Retrieved 28 April 2018.)

4.5 CONCLUSION

Psychoactive drugs affect the body’s central nervous system. With the ability to change

the brain’s functionality, they quickly alter mood, perception, and consciousness.

Consequently, some of the drugs that fall under this category are habit-forming.

Particularly, these include stimulants like cocaine and depressants like alcohol.

Unfortunately, becoming chemically dependent on a substance could potentially lead to

addiction.

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 CHAPTER FIVE

5.0 REGULATION AND CONTROL

The legality of psychoactive drugs has been controversial through most

of recent history; the Second Opium War and Prohibition are two historical examples of

legal controversy surrounding psychoactive drugs. However, in recent years, the most

influential document regarding the legality of psychoactive drugs is the Single

Convention on Narcotic Drugs, an international treaty signed in 1961 as an Act of

the United Nations. Signed by 73 nations including the United States, the USSR,

Pakistan, India, and the United Kingdom, the Single Convention on Narcotic Drugs

established Schedules for the legality of each drug and laid out an international

agreement to fight addiction to recreational drugs by combatting the sale, trafficking,

and use of scheduled drugs. (United Nations Single Convention on Narcotic Drugs. Archived 2008-
05-10 at the Wayback Machine Retrieved on June 20, 2007.)

In the United States, the Food and Drug Administration (FDA) has authority over all

drugs, including psychoactive drugs. The FDA regulates which psychoactive drugs

are over the counter and which are only available with a prescription. (History of the Food
and Drug Administration.)

In the medical context, psychoactive drugs as a treatment for illness is widespread and

generally accepted. Little controversy exists concerning over the counter psychoactive

medications in antiemetics and antitussives. Psychoactive drugs are commonly

prescribed to patients with psychiatric disorders. However, certain critics believe that

certain prescription psychoactives, such as antidepressants and stimulants, are

overprescribed and threaten patients' judgement and autonomy. (Manninen, B A (2006).

21
5.1 REGULATORY MEASURES

During the 20th century, many governments across the world initially responded to the

use of recreational drugs by banning use, production, or distribution of them, and

making their use, supply, or trade a criminal offense. A notable example of this

was Prohibition in the United States, where alcohol was made illegal for 13 years.

However, many governments, government officials, and persons in law enforcement

have concluded that illicit drug use cannot be sufficiently stopped through

criminalization.

The existing drug policies have failed in their intended goals of addressing the problems

of crime, drug abuse, addiction, juvenile drug use, stopping the flow of illegal drugs into

this country and the internal sale and use of illegal drugs. By fighting a war on drugs, the

government has increased the problems of society and made them far worse. A system

of regulation rather than prohibition is a less harmful, more ethical and a more effective

public policy

5.2 CONCLUSION

Among the few analysts that have written seriously on this issue of regulating new

psychoactive drugs intended for recreational use, there is considerable unease with the

existing system for making decisions about newly emerging psychoactive substances. A

research effort to improve understanding of the substitution effects of new entities, as

well as an examination of how prohibition of these entities creates market harms, would

go a long way toward clarifying the issues

22
6.0 DISCUSSION

Drug use and addiction cause a lot of disease and disability in the world.

Recent advances in neuroscience may help improve policies to reduce the harm that the

use of tobacco, alcohol, and other psychoactive drugs impose on society.

Pure psychoactive drugs and direct routes of administration are evolutionarily novel

features of our environment. They are inherently pathogenic because they bypass

adaptive information processing systems and act directly on ancient brain mechanisms

that control emotion and behavior. Drugs that induce positive emotions give a false

signal of a fitness benefit. This signal hijacks incentive mechanisms of "liking" and

"wanting," and can result in continued use of drugs that no longer bring pleasure. Drugs

that block negative emotions can impair useful defenses, although there are several

reasons why their use is often safe nonetheless. A deeper understanding of the

evolutionary origins and functions of the emotions and their neural mechanisms is

needed as a basis for decisions about the use of psychoactive drugs. (R M Nesse, 1997)

6.1 CONCLUSION

It is an undeniable fact that psychoactive substances pose various hazards for the user.

Emerging technologies and therapies to prevent and treat dependence and related

problems pose difficult ethical issues. These issues should be addressed by national and

international scientific and policy communities as a priority.

23
 REFERENCES

A. Dietrich, in Encyclopedia of Consciousness, 2009

AJ Giannini, RQ Quinones, DM Martin. Role of beta-endorphin and cAMP in addiction

and mania. Society for Neuroscience Abstracts. 15:149, 1998

"Are addictions classified as being a mental health disorder?". YouTube. 16 September

2020. Archived from the original on 11 November 2021. Retrieved 21

December 2020

Australian Government Department of Health. Types of Drugs - Drug catagories 2019

[12.01.2021

Azzam AAH, McDonald J, Lambert DG. Hot topics in opioid pharmacology: mixed and

biased opioids. Br J Anaesth. 2019 Jun;122(6):e136-e145. [PubMed]

Boyland E, Chasseaud LF. The role of glutathione and glutathione S-transferases in

mercapturic acid biosynthesis. Adv Enzymol Relat Areas Mol Biol. 1969;32:173-
219

Boys, A., Fountain, J., Marsden, J., Griffiths, P., Stillwell, G. and Strang, J.

(2000a) Drug Decisions: A Qualitative Study of Young People, Drugs and Alcohol.

Health Education Authority, London.

Brands B, Sproule B, Marshman J, Ontario. Addiction Research F. Drugs & drug

abuse : a reference text. Toronto, Ont.: Addiction Research Foundation; 1998

[cited 2021 May]

24
Commandeur JN, Stijntjes GJ, Vermeulen NP. Enzymes and transport systems involved

in the formation and disposition of glutathione S-conjugates. Role in

bioactivation and detoxication mechanisms of xenobiotics. Pharmacol Rev. 1995

Jun;47(2):271-330.

Cornelis MC. The Impact of Caffeine and Coffee on Human Health. Nutrients. 2019 Feb
16;11(2

Crabbe JC, Rigter H, Uijlen J, Strijbos C. Rapid development of tolerance to the

hypothermic effect of ethanol in mice. Journal of Pharmacology and
Experimental Therapeutics. 1979;208:128–133

Damasio A, Damasio H, Tranel D. (2013) Persistence of feelings and sentience after

bilateral damage of the insula. Cereb Cortex. 23(4):833-46. doi:
10.1093/cercor/bhs077. PMID: 22473895

El-Seedi et al., 2005; Guerra-Doce, 2015; Li, 1973

Garza AZ, Park SB, Kocz R. StatPearls [Internet]. StatPearls Publishing; Treasure Island
(FL): Jul 4, 2023. Drug Elimination. [PubMed

Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present--a
pharmacological and clinical perspective. J Psychopharmacol. 2013
Jun;27(6):479-96

History of the Food and Drug Administration. Retrieved at FDA's

website Archived 2009-01-19 at the Wayback Machine on June 23, 2007.

25
Kalant H. Research on tolerance: What can we learn from history? Alcoholism: Clinical
and Experimental Research. 1998;22:67–76.

Leo E. Hollister, Psychoactive drugs in historical perspective, 1972

Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive
Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A
Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill
Medical. pp. 364–368

Manninen, B A (2006). "Medicating the mind: A Kantian analysis of overprescribing

psychoactive drugs". Journal of Medical Ethics. 32 (2): 100–
5. doi:10.1136/jme.2005.013540. PMC 2563334. PMID 16446415

Merlin, M.D (2003). ‘Archeaological Evidence for the Tradition of Psychoactive Plant

Use in the Old World

Nestler EJ (August 2016). "Reflections on: "A general role for adaptations in G-Proteins

and the cyclic AMP system in mediating the chronic actions of morphine and

cocaine on neuronal function"". Brain Research. 1645: 71–4

Ramsay, M. and Partridge, S. (1999) Drug Misuse Declared in 1998: Results from the

British Crime Survey. Home Office, London.

Rohsenow DJ, 1990 – 1991) Rohsenow DJ, Niaura RS, Childress AR, Abrams DB, Monti
PM. (1990-1991) Cue reactivity in addictive behaviors: theoretical and
treatment implications. Int J Addict. 25(7A-8A):957-93. DOI:
10.3109/10826089109071030. PMID: 2131326

26
Sagar, K.A. , Dahlgren M.K., Gö nenç A., et al 2015. The impact of initiation: early
onset marijuana smokers demonstrate altered Stroop performance and brain
activation. Dev. Cogn. Neurosci. 16: 84–92.

"Supporting mothers with opioid addiction is the best bet in fighting neonatal

abstinence syndrome". sheknows.com. 10 May 2017. Archived from the original

on 11 November 2017. Retrieved 28 April 2018.

United Nations Single Convention on Narcotic Drugs. Archived 2008-05-10 at

the Wayback Machine Retrieved on June 20, 2007.

United States Food and Drug Administration. CDER Data Standards

Manual Archived 2006-01-03

Volkow, N.D. , Wang G.‐J., Fowler J.S., et al 2011. Addiction: beyond dopamine
reward circuitry. Proc. Natl. Acad. Sci. USA 108: 15037–15042.

Volkow, N.D. , Fowler J.S., Wang G.‐J. & Goldstein R.Z.. 2002. Role of dopamine, the
frontal cortex and memory circuits in drug addiction: insight from imaging
studies. Neurobiol. Learn. Mem. 78: 610–624

Wilde M, Pichini S, Pacifici R, Tagliabracci A, Busardò FP, Auwärter V, Solimini R.

Metabolic Pathways and Potencies of New Fentanyl Analogs. Front
Pharmacol. 2019;10:238.

27