Beyond the high: Exploring addiction to non-psychoactive substances

Concept of non-psychoactive substance use in the diagnostic and statistical manual of mental disorders (DSM-5)

• Substance use disorder (SUD) in DSM-5 combines the DSM-IV categories of substance “abuse” and “dependence” into a single disorder measured along a single continuum. Severity specifiers based on the fulfillment of 11 diagnostic features of SUD have also been incorporated: Mild (2 or more), moderate (4 or more), or severe (6 or more).^[5]

• Apart from the substances that the International Classification of Diseases (ICD) covers, DSM-5 categorizes OTHER (or UNKNOWN) substance-related disorders (292.9), wherein it incorporates anti-Parkinsonian medications, nitrous oxide, betel nut, and kava. It also considers culture-related issues that may be associated with the use of indigenous substances within a cultural region.^[6]

Genetics

Hereditary factors play a significant role, accounting for an estimated 40–60% of addiction risk. Individuals with an addictive personality may be more prone to various addictions.

Environment

Environmental factors, such as parental neglect, abuse, and peer pressure, contribute to addiction risk. Avoiding triggering situations or people is often necessary for those in recovery.

Dual diagnosis

The term “dual diagnosis” is used for individuals who have both an addiction and a mental health disorder. Addiction can be exacerbated by underlying mental health issues, creating a vicious cycle with negative consequences. Likewise, medical conditions can also increase one’s risk of addiction. An individual taking prescription pain pills after surgery may develop an addiction to them. Furthermore, it is also possible for an injury or illness to drastically change a person’s lifestyle, leading to a dependency on drugs or alcohol as a coping mechanism.

Drug type and method of administration

The substance abused and its method of administration influence the speed and severity of addiction. The faster the addiction progresses, the worse the outcome, including a fatal overdose. The drug’s route of administration can also influence addiction, as some drugs enter the bloodstream and brain without being filtered by the liver, increasing the likelihood of addiction.

Early onset of addictive behavior

Addiction is more likely to develop when it starts early, potentially affecting brain development and increasing the risk of future mental health disorders.

Personality profile

High impulsivity and sensation-seeking, along with low harm avoidance, are associated with substance use and behavioral addictions such as internet addiction and gambling. Factors such as self-directedness and interpersonal conflict may contribute to internet addiction.^[9,10]

Nonsteroidal anti-inflammatory drug/pain killers/topical pain relief ointments

In recent years, addiction to prescription painkillers (oral/topical) has progressively increased owing to the easy availability of over-the-counter drugs. Possible reasons include:

• Regular use of pain medications results in increased drug receptors in the brain, followed by subsequent nerve cell degeneration.

• Taking opiates as a pain reliever prevents the body from producing endorphins (the body’s natural painkillers). When the brain’s nerve cells degenerate, physical dependence on opiates results, whereas dose reduction/drug cessation leads to withdrawal symptoms.^[11]

Anabolic steroids

Anabolic steroids are synthetically produced variants of the naturally occurring male hormone testosterone. Durabolin (Nandrolone), Deca-Durabolin (Nandrolone Decanoate), Equipoise (Boldenone undecylenate), and Winstrol (stanozolol) are some of the most abused anabolic steroids. Common street (slang) names for anabolic steroids include gym candy, pumpers, stackers, weight trainers, and juice. Bodybuilders, athletes, fitness buffs, and people requiring enhanced physical strength (bodyguards, construction workers, and law enforcement officers) often use anabolic steroids to boost their performance. In addition to increasing lean body mass, strength, and aggressiveness, steroids reduce recovery time between workouts, making it possible to train harder with greater strength and endurance. Non-athletes use steroids to build muscle mass and reduce body fat, which they believe improves personal appearance.^[12]

Laxatives

Historically, laxative use has been an integral part of medical therapy. However, they are widely abused, and people are becoming dependent on them.^[13] People habituated to using laxatives can be grouped as:

• First and foremost, 10–60% of patients with eating disorders tend to abuse laxatives (for inducing diarrhea) to feel thinner and lose weight by getting rid of unnecessary calories.^[14] They mistakenly believe that laxatives prevent calorie absorption and weight gain by rushing food and calories through their gut. This abuse sets up a vicious cycle of dehydration (secondary to fluid loss) and fluid retention (renin-angiotensin response to dehydration), resulting in reusing laxatives to dehydrate themselves and lose fluid weight. As bowel refractoriness sets in, laxative dose escalation is needed to get the same effect.^[15] Stimulants are the most abused laxatives due to relatively high fecal discharge compared to other laxatives.^[16]

• Second, middle-aged or elderly persons often use laxatives to relieve constipation but eventually end up overusing them to the point of bowel refractoriness.^[17]

• The third group consists of individuals involved in sports or athletic training with set weight limits. The sub-group here that has perhaps been best characterized includes wrestlers, who take laxatives to drop weight.^[18]

• Finally, there is a group of surreptitious laxative abusers who use it for the sole purpose of inducing factitious diarrhea.^[19]

Antidepressants

Most people taking antidepressants do not abuse them. However, certain classes of antidepressants do carry abuse potential. Vulnerable patient populations include those with a history of substance abuse and those in controlled environments. There were reports of MAOI (monoamine oxidase inhibitors) misuse from the 1960s to the 1990s. However, the most misused antidepressant over the past decade has been bupropion, which acts through dual inhibition of norepinephrine and dopamine reuptake, thereby increasing the intrasynaptic concentrations of these neurotransmitters. Bupropion sustained release activates the nucleus accumbens, a key component of the brain reward system implicated in the development of addiction. TCAs (tricyclic antidepressants) primarily inhibit serotoninnorepinephrine reuptake but also block the muscarinic receptors (producing anticholinergic effects), histamine receptors, and alpha-1 and alpha-2 receptors. Tertiary TCAs have prominent anticholinergic/antihistaminergic effects with resultant confusion and/or delirium when misused.^[20]

Herbal derivatives

The term “herb” refers to any plant that is grown for cooking, medicinal, or in some cases, for spiritual purposes. Certain plants can induce psychotic, stimulant, sedative, euphoric, and anticholinergic effects when abused. Such herbal substances that induce a high should be labeled as “dangerous” due to their potential for addiction and cognitive decline with prolonged use.^[21]

Hallucinogens

• Salvia divinorum: The active ingredients of S. divinorum include diterpene and salvinorin-A (k-agonist). When smoked, its effect appears within 1 min and lasts for 15 min or less. It causes psychedelic-like changes such as mood fluctuations, altered perceptions, somatic sensations, and alterations in the perception of external reality and the self.^[22]

• Nutmeg: The active ingredients of nutmeg include eugenol, borneol, linalool, and many amphetamine derivatives, which have psychotropic and sympathomimetic effects lasting up to 24 h.^[23] When taken in large doses, nutmeg can be potentially dangerous, causing dizziness, nausea, hot flushes, dry mouth, tachycardia, urinary retention, and constipation. Ingestion of large quantities of nutmeg can lead to “Nutmeg poisoning,” an acute psychiatric disorder characterized by fear of impending doom and/or agitation.^[24] There is no specific antidote for nutmeg poisoning, and treatment comprises symptomatic and supportive care.

Anticholinergics

• Datura stramonium: Also known as Jimson weed, angel’s trumpet, devil’s weed, thorn apple, tolguacha, stinkweed, and moonflower. The active ingredients of Datura include atropine, hyoscyamine, and scopolamine. Mostly abused for its hallucinogenic and euphoric effects, Datura may sometimes cause anticholinergic intoxication, resulting in classic antimuscarinic symptoms due to competitive blockade of acetylcholine at the central and peripheral muscarinic receptor sites. Treatment comprises supportive care, gastrointestinal decontamination (i.e., emesis and/or activated charcoal), and physostigmine in severe cases.

• Ephedra alkaloids: Ephedra (derived from the plant Ephedra sinica) has long been used as an herbal remedy in traditional Chinese medicine to treat asthma, hay fever, and the common cold.^[25] For centuries, Mormons have consumed an ephedra-containing beverage known as “Mormon tea” for its stimulant effect. More recently, it has been used in the form of dietary supplements to boost energy and alertness, enhance athletic performance, and promote weight loss. Ephedra-related toxicity (like other central nervous system stimulants) is treated by addressing central sympathomimetic stimulation, cardiovascular toxicity, and secondary complications caused by the heightened energy state associated with sympathetic stimulation.

• Betel nut: Nearly 10% of the world population chews betel nuts (Areca catechu), the fourth most abused substance globally after caffeine, alcohol, and nicotine. The areca nut contains tannin, gallic acid, a fixed gum oil, lignin, traces of terpineol, and three main alkaloids, namely arecoline, arecaidine, and guvacine. The pharmacological effects of betel nut are attributed to the alkaloid arecoline, which acts as a cholinomimetic agonist at nicotinic and muscarinic receptors and as a potent inhibitor of the enzyme acetylcholinesterase.^[26] No specific antidote is present for toxicity.

• Yohimbine: A stimulant and aphrodisiac, yohimbine is an alkaloid obtained from the bark of Pausinystalia yohimbe, Corynanthe yohimbe, and Rauwolfia serpentina (Indian Snakeroot). It is marketed as a supplement for bodybuilding, sexual enhancement, and erectile dysfunction despite limited evidence regarding its efficacy.^[27]

• Kava: The drug kava lactones (or pyrones) are derived from the dried roots and rhizome of Piper methysticum. Many South Pacific countries use Kava extract in traditional recreational drinks, whereas in Western societies, it is used as an over-the-counter anxiolytic, muscle relaxant, mood enhancer, or treatment for premenstrual syndrome. Kava enhances the effect of other centrally acting agents such as alcohol and benzodiazepines. Long-term use of kava, especially in high doses (400 mg of kava pyrones daily), has been associated with the development of dry, flaky, yellow skin (kava dermopathy) through an unknown mechanism; the effect may be reversible upon cessation of the drug.^[28]

Clove cigarettes

With approximately 30% cloves (Syzygium aromaticum) and 70% tobacco, clove cigarettes contain twice as much tar, nicotine, and carbon monoxide as average cigarettes. There is a misconception among many users that clove cigarettes are herbal/natural alternatives to tobacco. Some are drawn to clove cigarettes in pursuit of “exotic” and unusual experiences. Eugenol, an ingredient in cloves, upon inhalation causes numbness in the throat along with a topical anesthetic effect. In the United States, “Toking” is the most common technique for obtaining enhanced pleasure from clove cigarettes through deep inhalation and increased retention of the smoke. The increasing use of clove cigarettes as a gateway drug among adolescents is quite concerning.^[29]

Absinthe

It is an alcoholic beverage made from the extracts of wormwood (Artemisia absinthium), a native European plant that has been naturalized in the United States. Chronic use of absinthe has been linked to “Absinthism,” a condition characterized by hyperexcitability and hallucinations. “Thujone,” a terpene found in the oil of wormwood, is believed to cause these hallucinatory experiences and/or psychosis.^[30]

Diuretics

Clinically, diuretics are used to treat hypertension and other cardiovascular disorders. Diuretics are classified as masking agents on the “WADA (World Anti Doping Agency) Prohibited List” due to their illegal use by sportspersons for weight loss and masking (to hide the effects of other prohibited substances).^[31] The majority of doping in sports involves the use of diuretics before an anti-doping test. Diuretics increase urine volume and dilute any doping agents as well as their metabolites present in urine, making their detection more difficult by the usual anti-doping tests. Athletes who use diuretics can quickly lose body weight, which is clearly advantageous in sports such as wrestling, boxing, judo, and weightlifting. Female gymnasts and ballet dancers also use diuretics to maintain a low body weight. Caldwell et al. compared the effects of exercise, sauna, and diuretic-induced acute dehydration on weight loss.^[32]

Vitamins

Vitamins play a crucial role in maintaining health and strength. An adequate diet is the only way to achieve a full vitamin intake. This is true for many reasons: First, there is no chemical diet that could contribute to the positive effects of a natural diet. Second, concentrated vitamins are far more expensive than their natural counterparts. Furthermore, people get tired or careless about taking pills, while they must always continue to eat food. Vitamin therapy is, however, necessary for the treatment of deficiency states, especially when severe. A physician must prevent their patients from becoming victims of needless and expensive vitamin therapy and psychoeducate them that vitamins are not a panacea for all human ills.^[33]