Which of the following is a psychoactive drug?

5.6 Synapses and receptors are traffic control points

Psychoactive drugs typically focus on one specific step in synaptic signaling. Thus l-dopa is prescribed for Parkinson's patients to increase a precursor for dopamine – an ingredient needed in the manufacture of the neuromodulator dopamine. Since Parkinson's disease involves the die-off of dopaminergic neurons in the substantia nigra, l-dopa will stave off its worst effects for some time. (Ultimately, the cells will have to be replaced, however, and much current research is focused on trying to implant dopaminergic cells in the substantia nigra (SN).)

In other cases, the effort is to keep a neurotransmitter dwelling longer in the synapse, so that it can repeatedly stimulate the postsynaptic membrane. A famous example is the selective serotonin reuptake inhibitors (SSRIs) – psychoactive drugs that are effective against depression and other disorders. Reuptake is the rather awkward term for recycling serotonin to the cell of origin, and if you can inhibit recycling you can keep the neurotransmitter around longer.

Gaba-ergic drugs like the benzodiazepines increase the amount of GABA in inhibitory synapses in the brain. And we should not forget the role of healthy diets, which supply all of the basic chemistry of the brain, mostly in the form of precursor chemicals, the raw materials from which the cells make all the specific proteins and other products they need.

A great deal of medical research is constantly trying to identify more traffic control points in the body and brain. Channel blockers work by inhibiting the flow of ions like calcium, sodium, and potassium across the cell membrane (important in cardiology as well as brain disorders). These are useful points to keep in mind. While the details are awesomely complex, the basic ideas are actually quite simple.

There are many kinds of neurons and neuron-like signaling cells. Neuroglia were traditionally thought to be only support cells for neurons, but have since been found to do their own transmission and computation. They outnumber neurons by a factor of ten. (The word glia originated from the Greek word for the glue between neurons.)

Introduction

Worldwide debate continues regarding the best way to control the use of psychoactive substances. The distinction between currently legal and illegal drugs is not based on any analysis of the benefits of the drug or the best way to maximize the positive aspects and reduce harms. There is an increasing recognition that criminal justice tools, in isolation, are ineffective to manage the criminal, health, and social problems associated with illegal drug use (Bertram et al., 1996). Evidence suggests that drug prohibition not only fails to address the problems, but also produces significant negative health and societal impacts. To address the problems created by drug prohibition the concept of a regulated market for all currently illegal drugs is being developed. This concept has grown out of the harm-reduction movement in which services are provided to active drug users without requiring abstinence (Health Officers Council of British Columbia [BC], 2005) Regulated market models are based on both public health and human rights principles that recognize psychoactive drug use as being a choice made by many people around the world.

Abstract

Psychoactive drugs are often used as a means of “escaping” from dreadful moments and stressful life events. Active-duty military personnel experience great deals of stress as a result of their commitment to the armed forces. For many, a less healthy approach at dealing with stress may be selected—one that involves coping through drug and alcohol use. Alcohol, tobacco, and illicit drug use are all prominent among the United States military. After implementing drug screening that detects illegal substances through urinalysis, means of coping with stress and rigors of active duty may have shifted to “legal highs.” Synthetic cannabinoids and synthetic cathinones, also known as “designer drugs,” contain modified molecular structures resembling those of illegal or controlled substances. These designer drugs are chemically structured in a way which allows users to experience a high similar to that of the analogous street drug (eg, marijuana for synthetic cannabinoids, methamphetamine or cocaine for synthetic cathinones), but that does result in failed drug tests. The current chapter focuses on drug abuse trends among US military personnel, more specifically designer drug use among US active-duty soldiers, and the policies that have been developed.

Overdose

Psychoactive drugs are often used for intentional self-poisoning and are the most common suicide methods in non-lethal suicide attempts and the third most frequent in fatal suicides. Investigators analyzed cases of suicidal self-poisoning from 2000 to 2010 from the national poisons center database and compared with cases of suicide documented in the project “Suicides, a national survey”. All cases with single substance exposure to a psychoactive drug (antidepressants, mood stabilizers, antipsychotics, sedatives) were included in the analyses. Opioids, over-the-counter and illicit- drugs were excluded from the analysis. A mortality index was calculated by the ratio of the number of suicides and the sum of all (lethal and non-lethal) suicide attempts. The investigators found that tricyclics had a higher mortality rate than other antidepressants, which is supported in previous literature. Interestingly among the sedatives, zolpidem had a higher mortality index compared to benzodiazepines. This may be due to its increased suicidal ideation and increasing reports of fatal intoxications. Clozapine and levomepromazine were found to be the most lethal antipsychotics due to high toxicity and clozapine is reserved for treatment resistant schizophrenia (Pfeifer et al., 2020) [c].

The authors want to highlight caution on the relative toxicity of psychotropic drugs and their risk of poisoning with suicidal intent.

A 15-year-old male patient was admitted to the hospital presenting with coma and limb convulsion after he had ingested 100 amitriptyline tablets (25 mg/tablet). The hospital performed direct hemoperfusion, rehydration, and antiepileptic treatments. The patient had a GCS score of 6/15, with bilateral pupil diameter of 4.0 mm, slow light reflexes, paroxysmal limb tics, fever of 38.5 °C, sinus tachycardia, and a BP of 120/80 mm Hg. The patient's blood gas analysis showed pH 7.40, PCO2 34.20 mm Hg and PO2 103.00 mm Hg. His liver and kidney function were in the normal range. After admission, continuous GI decompression obtained 300 mL of green gastric material. After 6 h, hemoperfusion performed again, and phenobarbital antiepileptic therapy administered at the same time. After 12 h of treatment, the pupil diameter of the patient was restored to 3.0 mm, and the patient became sensitive to light relaxation. The patient restored consciousness after 24 h of treatment. The patient was discharged 7 days later with a GCS score of 15, and stable vital signs. The investigators concluded hemoperfusion therapy should be used as early as possible in suspected amitriptyline overdose situations (Wu et al., 2020) [r].

The authors emphasize the dangers of overdose situations of amitriptyline.

Hallucinations

Psychoactive drugs are numerous but are difficult to separate clinically. A useful grouping of drugs is derived from Pradham (18), abbreviated here:

Ergot Derivatives:

Lysergic acid diethylamine (LSD).

Dimethyltryptamine (DMT).

Psilocybin.

Cannabanoids:

Marijuana.

Tetrahydrocannabinol (THC).

Phenylalkylamines:

Mescaline.

Amphetamines.

DOM.

MDA.

Atropine.

Scopolamine.

Hyoscine.

Others:

Phencyclidine (PCP).

Nutmeg.

Small children may overdose on these drugs. Amphetamines and related drugs are discussed elsewhere. Three drugs are discussed here, although hallucinations may not be the presenting or dominant symptom (and are usually absent in marijuana use).

Behavioral Toxicity

Psychoactive drugs, both licit and illicit, can cause alterations in perception, judgment, coordination, mood, and information processing. In cases involving violence or accidental trauma, when such drugs are detected in the body of the deceased, questions inevitably arise regarding the role of the drug(s) in precipitating the fatal event. The issues are similar to those in human performance toxicology, except that specimens are usually collected postmortem rather than from a living subject. Therefore, drug concentrations must be considered in light of postmortem changes, and impairment or intoxication must be deduced from factual evidence (eyewitnesses) and physical evidence available at the scene where the fatal incident occurred. For example, a motor vehicle crash investigation may discover evidence of driver error, and later toxicological analysis reveals elevated blood alcohol or a high concentration of a drug with the potential to cause impairment. Similarly, when a person becomes excited, violent, and irrational, then disrobes, breaks objects, struggles with police, and suddenly becomes unresponsive and dies, a finding of even a few hundred nanograms per milliliter of cocaine in the blood of the deceased suggests that the death or behavior can be attributed to cocaine-induced excited delirium. This opinion is supported by a documented high postmortem body temperature and a postmortem blood benzoylecgonine concentration of several thousand nanograms per milliliter.

Because of the many factors affecting measured postmortem drug concentrations, such data can rarely serve as the sole basis for interpretation. They must be correlated with evidence from the autopsy and with information gathered by police, and other investigators. Conversely, inferences and suspicions derived from autopsy and investigation must be refined and confirmed through toxicological studies. Only then can reliable opinions be formulated regarding the role of drugs or poisons in a death investigation.

Drug Classification

Psychoactive drugs are compounds that act on the central nervous system and alter behavior and cognition. They are highly lipophilic and thus readily cross the blood–brain barrier that keeps neurons protected from circulating blood. 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 nonbehavioral effects that are often far more dangerous to health, and, in some instances, can be lethal.

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. This scheme classifies these drugs into four broad classes.

The first are the sedatives and hypnotics. Drugs in this class depress or inhibit brain activity and produce drowsiness, sedation, or sleep; relieve anxiety; and lower inhibition. Although depressants do not share a common neural mechanism, most of them either decrease the metabolic activity in the brain or increase the transmission of the principal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). All sedative compounds have the potential for addiction and dependency. Common examples include barbiturates, such as Seconal; benzodiazepines, also known as minor tranquilizers, such as Xanax or Valium; nonbarbiturate sedatives, such as methaqualone; nonbenzodiazepines, such as buspirone; antihistamines and anesthetics; and alcohol. In low doses, alcohol can act as a stimulant, but with increased dosage its main effects are almost always depressive. Marijuana, which is derived from the hemp plant Cannabis sativa, is often misleadingly classified in the category of psychedelic. Given that its most pronounced behavioral symptom is sedation and the fact that it rarely produces – and only in very high doses – sensory distortions of hallucinatory quality, it is also best categorized here as a sedative.

The second class are stimulants. These drugs produce behavioral and mental arousal. This class of psychoactive compounds also includes a variety of different substances each of which may also have a different neural mechanism. Common examples are amphetamines; cocaine; the methylxanthines, such as caffeine which is the most widely used psychoactive drug in the world, theophylline, which is present in tea, and theobromine, the psychoactive ingredient in chocolate; nicotine or tobacco; appetite suppressants; and a variety of exotic plants, such as the betel nut, khat, yohimbe, and ephedra. Stimulants vary in strength, legal status, and the manner in which they are taken; however, all stimulants have addictive potential. None of these preparations, however, induces radical changes to mental status, such as, for instance, hallucinations or delusions, except perhaps cocaine and amphetamines when taken in high doses.

The third class consists of the opiates. Drugs in this class act on opiate receptors and their two main effects are that they mediate relief from pain and produce feelings of euphoria, which is experienced in a dreamlike state of consciousness. It is also these two effects, of course, that make them drugs of abuse. In pharmacology, the term narcotics, derived from the Greek word for stupor, is used interchangeably with opiates but the legal systems in most countries use the term narcotics to refer to all illicit drugs, regardless of their mechanism of action. Opiates are highly addictive and can either be natural, semisynthetic, or synthetic. Natural opiates such as opium are derived from the opium poppy. The active ingredients of opium are morphine and codeine. The most famous semisynthetic opiate is heroin, which is two hundred times more potent than morphine. If taken intravenously, heroin produces what is known as a rush, an intense feeling of pleasure of euphoria that, according to first-hand reports, is not comparable in strength to any other experience. This makes heroin the most psychologically addictive drug known. Examples of synthetic opiates, also known as designer drugs, include methadone, naloxone, and the prescription pain medication Demerol, which is the drug most abused by physicians.

The fourth and last class consists of the hallucinogens and psychedelics. Drugs in this category share the common feature that they induce hallucinations or have other ‘mind manifesting’ or ‘expanding’ properties. But this is also where the commonality ends. Pychedelics can either occur naturally in a plant, such as mescaline, which is derived from the peyote cactus, or be synthesized in the laboratory, such as LSD. In the latter case, such drugs are also known as designer drugs. In terms of consciousness – or behavior, for that matter – no overarching framework seems to be emerging that can organize their wide-ranging, phantasmagoric effects. Pharmacologically, they are also all over the place. For every classical neurotransmitter system, there is a drug in this class. In consequence, psychedelics are probably best classified according to the neurotransmitter system they primarily affect. Cholinergic psychedelics include, most prominently, physiostigmine, scopolamine, and atropine, which are well known to cause bad trips. Drugs that alter norepinephrine transmission include mescaline and the popular ecstasy (MDMA), which cannot be said to cause bone fide hallucinations. Drugs that alter serotonin transmission include lyseric acid diethylamide or LSD, psilocybin, and morning glory. These drugs are perhaps most commonly associated with the psychedelic experience. There are also drugs with psychedelic properties that alter dopamine (cocaine), glutamate (ketamine), GABA (muscimol), opioid (morphine), or cannabinoid (hashish) transmission; however, these preparations are not predominantly hallucinogenic and they are best classified elsewhere according to their respective main effect. A peculiar subclass of the hallucinogens and psychedelics category are the psychedelic anesthetics, such as phencyclidine or PCP (angel dust), ketamine, and several gases and solvents, such as ether or nitrous oxide. With the exception of the cholinergic psychedelics, all drugs in this class have a high margin of safety, that is, a high TI and are generally nonlethal – even when taken in large quantities.

In addition to these four broad categories, there a number of other drugs that affect the mind. These compounds are used to treat a variety psychological and neurological disorders and include antidepressants; antipsychotic medication, such as clozapine, chlorpromanzine, and haloperidol; and drugs for epilepsy, Parkinson’s disease, the dementias, such as Alzheimer’s disease, and spasticity.

In most countries, the legal system takes a different approach to classifying psychoactive drugs. In the United States, for instance, the Comprehensive Drug Abuse and Prevention and Control Act of 1970 regulates these substances. According to this scheme, drugs are classified into five schedules according to the perceived risk of developing dependency to that drug. Schedule I drugs such as heroin, marijuana, and most psychedelics have a high risk of dependency and no accepted medical use. These drugs are forbidden and cannot be obtained by prescription or, often, even for research, for that matter. Schedule II drugs, such as morphine, codeine, amphetamines, and certain barbiturates have a high risk of dependency but are accepted by the medical community for some treatment, that is, they have a medicinal purpose. Schedule III drugs have a risk of moderate physical dependency or high risk of psychological dependency and include preparations with limited opiates (e.g., morphine) and barbiturates not included in Schedule II. Schedule IV drugs, such as the benzodiazepines, have a slight risk of mild physical or psychological dependency. Schedule V drugs have less risk of mild physical or psychological dependency. Finally, alcohol and tobacco are not classified under this law. They fall under the jurisdiction of the Alcohol, Firearms, and Tobacco agency, which is a division of the US Department of Treasury.

This is as good a place as any for a note of caution. Most explanations on the neural basis of altered states rely solely on neurochemical modulation. The reason for this is that drugs are the most common way to induce altered states and their known mechanism of action for changing brain function was for a long time the only hope to find a sound, mechanistic explanation for the mercurial nature of ASC. But there is a danger of leaning too hard on neurochemistry. An increase in serotonin does not cause happiness any more than an excess of dopamine causes paranoid schizophrenia. Neurotransmitters per se do not carry content in their messages. Drugs that work on the same neurotransmitter system, even via the same synaptic mechanism, can have very different effects on consciousness (Table 1). Prozac, for instance, increases serotonergic transmission and is a well-known antidepressant. LSD, on the other hand, is also a serotonergic agonist. LSD, however, sends you on a trip of some kind, but it certainly is not an antidepressant. Similarly, cocaine is a dopaminergic reuptake blocker and produces alertness and euphoria. Ritalin, the treatment of choice for children with attention deficit hyperactivity disorder (ADHD), works on exactly the same neural mechanism, blocking the reuptake of dopamine. Cocaine gets you high, though, to say nothing of prison, while Ritalin has a calming effect and the medical community has approved it to be administered to kids. The moral here is this. Behavioral pharmacologists have long given up on the naive idea that complex psychological phenomena can be attributed to changes in the concentration of a simple little molecule. Every transmitter system can be modulated by drugs that do and do not alter consciousness. As such, we must also consider the function of the neural structure in which the changes in chemical neurotransmission occurs.

Table 1. A sampler of psychoactive drugs detailing some of the more interesting effects on consciousness

CategoryDrug and originMechanism of actionPhenomenologySedatives and hypnoticsValiumBinds to benzodiazepine site of the GABAa receptor facilitating the effects of GABAProduces all degrees of behavioral depression from sedation, to relaxation, to coma; reduces anxiety, disinhibition, sleepiness, tiredness, sense of well-beingAlcoholBinds to barbiturate site of the GABAa receptor facilitating the effects of GABARelief of anxiety, sedation, disinhibition. Stimulant in low doses. Impairments in vision, speech, motor control, and judgmentMarijuana (Cannabis sativa)Receptor agonist on the CB1 receptor; also inhibits 5-HT3 receptorsMain effects are sedation and analgesia; others include heightened sensations, uncontrollable laughing, sense of well-being, intensified introspection, mental slowingStimulantsAmphetamineStimulates the release of DA and blocks its reuptake; also activates adrenergic receptorsAlertness, arousal, insomnia, loss of appetite, and combats fatigue; known as ‘speed’ when taken IV or as ‘speedball’ in combo with opioids (to reduce side effects)Cocaine (Coca plant)DA reuptake blockerSame as for amphetamines; more euphoria and paranoia; freebasing and crack result from purification procedures and intensify the experience, especially the euphoriaOpiatesMorphine, heroin (opium poppy)Activates opioid receptorsAnalgesia, peacefulness, feelings of warmth and well-being, boundless energy, dreamy imagery; when taken IV, heroin induces a ‘rush’ of intense pleasure that is without equalHallucinogens and psychedelicsScopolamine, atropine (Nightshade)Cholinergic antagonistRestlessness, delirium, vivid hallucinations, disconnection with reality, no memory of the experience; OBEs are common; bad trips can easily be filled with ugly monstersMescaline (Peyote cactus)In a class of its own; structurally related to NE and alters NE transmissionVivid hallucinations consisting of bright colors, geometric designs, and animals; synesthesia; no OBE, insight is retained; more color and less form distortion than LSDMDMA (Ecstasy)Pharmacologically promiscuous but primarily stimulates the release and blocks the reuptake of 5-HT2Induces feelings of empathy and sympathy; creates desire for intimacy and need for personal contact, heightens self-awareness; no hallucinations or loss of realityLSDActivates 5-HT2a receptorsVivid, kaleidoscopic sensory changes (e.g. mosaic patterns on all surfaces), powerful feeling of love, mystical oneness, synesthesia; bad trips include anxiety, panic, violencePsilocybin, psilocin (Mushrooms)Structure resembles 5-HT and activates 5-HT receptorsPleasant feelings of relaxation, distortions of space, visual hallucinations with more intense color than LSD; effects resemble more mescaline than LSD; fewer bad tripsDMT (Virola tree)5-HT agonistShort-acting and intense psychedelic rush (businessmen’s LSD); loss of all reality, overwhelming visual hallucinations; communication with Gods, spirits, or the deceasedPCP (Angel dust), ketaminePrimarily NMDA receptor agonists but also alter opioid and monoamine transmissionAnesthesia with depersonalization, loss of ego boundaries, changes in body image, floating, OBE, NDE, distortion of time and space, full amnesia, euphoria; frequent bad trips

Dietrich A, Introduction to Consciousness, 2007, Palgrave Macmillan, reproduced with permission of Palgrave Macmillan.

3 Conclusions

Psychoactive drugs, used for nonmedical purposes, can produce a range of pleasant feelings, from mild stimulation to euphoria, to altered perception and elevated mood. These effects reinforce drug-seeking and consumptive behaviors. Yet these positive sensations, intoxication or euphoria, can result in a progressive brain disease with adverse consequences to individuals, to others and from “in utero to old age”. Research has been instrumental in clarifying the individual, genetic, environmental risk and protective factors associated with drug use and use disorders. It has revealed the immediate targets of drugs in the brain, dramatic adaptive changes to signaling systems, neuronal morphology, neural circuitry, genes and epigenetics, behavior after repeated exposure.

At a macrolevel, imaging research has shown a significant shift in the balance of neural circuitry that governs inhibitory control, emotional processing/regulation toward regions that promote compulsive, risk-seeking behaviors. Yet major voids in our understanding of biological effects of drug persist. If filled, these gaps could further shape public health policies for prevention, intervention, and treatment: why are adolescents more vulnerable to addiction? Is it largely because of the interaction of a drug during brain development or because of predisposing factors in the adolescent? Does the adolescent brain respond and adapt differently to drugs than the adult brain? Are drug-induced adaptive responses in adolescent brain more or less likely to be reversed in adulthood? Why are youth with psychiatric disorders (e.g. attention deficit hyperactivity disorder, oppositional defiant disorder) more likely to initiate drug use? Are specific brain changes at any age irreversible? Is irreversibility age-dependent? Do biological changes recover in tandem with cognitive and behavioral improvements during recovery? Longitudinal imaging research combined with psychosocial questionnaires from periadolescent to young adulthood would provide needed insight into these questions.

Why does a psychiatric disorder confer a high risk for a substance use disorder? Improved understanding of the reasons people with neuropsychiatric diseases are attracted to smoking, alcohol, and other drugs and changes that may uniquely affect the comorbid brain will clarify this question and conceivably offer improved intervention strategies. Given that there is a significant genetic component to drug use disorders, are there genetic markers with high predictive value for individuals? Markers may alert family members to the increased risk of initiating drug use. Can markers in biologically accessible fluids or tissues be identified for a substance use disorder that reflects disease and recovery? Such markers are needed to verify objectively the efficacy of treatment, and for a number of other purposes.

Ongoing research will provide further insight into substance use disorders, brain function and ease the coalescence of substance use disorders with mainstream medicine. The advent of CPT®, Medicare and Medicaid billing codes for SBIRT services, the extensive use of prescription opioids for nonmedical purposes and availability of office-based medications such as buprenorphine are promoting medicalization of what, in the past diverged into two separate systems of care.

Which of these drugs is a psychoactive drug?

Which of the following is a psychoactive drug quizlet?

What is the most popular psychoactive drug?

Which of the following is true of psychoactive drugs?