Addiction Treatment Blog

A hundred doses of happiness are not enough: send to the drug store for another bottle – and, when that is finished, for another…

Aldous Huxley (1894-1964), ‘Brave New World Revisited’.

Over-the-counter (OTC) medicines are defined as those which are available without prescription from a pharmacy. As is the case with prescription only medicines, it is important to distinguish between medicine abuse and unnecessary use. For example, many members of the public take vitamin and analgesic preparations indiscriminately. These are examples of unnecessary use of OTC medicines. Many products are also taken for inappropriate medical conditions of where there is little evidence of therapeutic benefit. Examples include vitamin C for colds and a large number of ‘alternative medicine’ products. In the context of this article, abuse implies use of a preparation for a non-medical purpose in order to achieve psychoactive effects (e.g. euphoria) or altered body-image (e.g. weight loss).

Reasons for OTC Abuse

Sometimes the abuse potential of an OTC product is discovered by chance while a patient is taking the preparation for a legitimate reason. Increasingly, however, people may experiment with OTC substances to try to find an effect to their liking. Rumours among the drug culture may alert abusers to a cheap, ready source of an alternative to street drugs. Sometimes, OTCs are used to ‘top-up’ or augment the effects of an illicit substance and occasionally they are used in an attempt to lessen or stave off withdrawal symptoms or for self ‘detoxification‘.

Certain abusers of OTC medicines are mentally ill and consume these products because of obsessive/compulsive disorder or other psychiatric condition.

Sympathomimetics

OTC sympathomimetic agents include pseudoephedrine, ephedrine, phenylephrine and phenylpropanolamine. They may be psychoactive if taken in large doses and probably act in a similar way to amphetamine, to which they are structurally related.

Most of the sympathomimetics have both direct and indirect actions on adrenergic receptors, i.e. they act by direct receptor stimulation and via an increased release of natural receptor agonists (dopamine and noradrenaline). Many OTC cough and cold products contain sympathomimetics and some examples are given in the table below. The preparations are usually taken orally.

Sympathomimetics are typically abused for one of the following reasons:

• to elevate mood and produce euphoria;
• as a substitute for amphetamine by regular users to alleviate craving;
• to combat fatigue;
• to cause weight loss;
• to enhance athletic stamina and performance;
• ephedrine can be used to manufacture more potent amphetamine-like drugs.

A study in 1992 showed that 11 out of 22 intravenous amphetamine abusers had used OTC sympathomimetics in the past year to avoid or reduce cravings for amphetamine. If taken regularly in large enough doses, sympathomimetics promote weight loss by suppressing appetite, as can amphetamines. However, weight loss tends to be small and transitory. Despite this, such products are sold to assist weight reduction in the USA. Large doses may also help to combat fatigue via central nervous system stimulation and OTC products of this kind are also openly marketed for this purpose in the USA.

Sympathomimetics are banned in competing athletes by the International Olympic Committee despite there being little evidence that these substances actually increase physical ability or stamina. Increased endurance might be expected by comparison with amphetamines but this has never been demonstrated.

It has been reported that ephedrine can be used to synthesise more potent amphetamines such as methamphetamine and methcathinone (’cat’). In the USA, this has led to the manufacturers of ephedrine being required to keep transaction records. Pharmacists who wish to sell ephedrine must register with the Drug Enforcement Agency and keep records of all tablet sales. The Drug Enforcement Agency estimated in 1995 that 100 tonnes of imported ephedrine were diverted into the clandestine synthesis of illicit drugs.

Sympathomimetics themselves possess weak amphetamine-like psychotropic effects; large doses can produce pleasant perceptual changes, euphoria and mental stimulation. One study has shown that 75 to 150 mg/kg ephedrine may elicit similar subjective and behavioural effects to 15 to 30 mg/kg amphetamine. Sometimes the abuse begins when patients taking these preparations for legitimate medical reasons discover the psychoactive effects by chance. In other cases, knowledge of the abuse potential of OTC products is passed from person to person at street level.

Children may be particularly sensitive to the psychoactive effects of sympathomimetics; hallucinations, agitation, nightmares and night terrors have been reported in infants given normal therapeutic doses.

The potential side effects of large doses of sympathomimetics include nausea and vomiting, tachycardia, palpitations, headache, insomnia, agitation, anxiety and anorexia. In addition, a number of case reports have described the advent of psychosis in association with abuse. In many ways, and not surprisingly, this is similar to ‘amphetamine psychosis‘. Symptoms tend to be paranoid in nature with feelings of persecution and are often accompanied by hallucinations. Psychosis may arise acutely after a single large dose or develop over long periods of time as a result of chronic high-dose administration. In either case, symptoms usually resolve within a few days of cessation, although long-lasting psychiatric problems can occur (but probably only in those suffering from mental illness or with a predisposition to it). Ephedrine has been most commonly linked to psychosis, the effect being seen at chronic doses as low as 125 mg per day.

Other rare adverse effects of high-dose sympathomimetics include tremor, intracranial haemorrhage, seizures, impotence and rhabdomyolysis.

Abuse of nasal preparations containing sympathomimetics is occasionally reported. Agents such as oxymetazoline are primarily alpha-adrenergic sympathomimetics but despite this more specific action they may share the potential for producing psychoactive effects. When taken for congestion, chronic use is often driven by the reflex nasal congestion which occurs upon discontinuation, such that administration must be repeated to relieve it.

The Chinese herbal preparation Ma Huang is prepared from the dried plant Ephedra sinica and related species. This naturally contains a quantity of ephedrine and has been the subject of abuse.

Examples of over-the-counter preparations containing sympathomimetics

Product	Sympathomimetic
Actifed	Pseudoephredine
Dimotane preparations	Pseudoephredine
Robitussin Chesty Cough with Congestion	Pseudoephredine
Sudafed	Pseudoephredine
Contac 400	Phenylpropanolamine
Day Nuse	Phenylpropanolamine
Eskornade	Phenylpropanolamine
Mu-Cron	Phenylpropanolamine
Sinutab	Phenylpropanolamine
Do-Do tablets	Ephedrine
Haymine	Ephedrine
Nirolex	Ephedrine
Dimotapp	Phenylephrine
Lemsip (certain preparations)	Phenylephrine
Beechams Hot Lemon (and some related products	Phenylephrine

Antihistamines

Abuse and dependence have been reported in particular for three drugs of this class: cyclizine, dimenhydrinate and diphenhydramine, although antihistamines such as chlorpheniramine and promethazine may be involved. The author is also anecdotally aware of attempted abuse of terfenadine.

The mechanism of action is unclear but the antimuscarinic properties of antihistamines become more prominent at high dose and this may be responsible for some or all of the abuse potential. Cyclizine also has some structural similarities to phencyclidine.

Cyclizine

Cyclizine is available OTC as Valoid and is also an important constituent of several prescription preparations (e.g. Migrill, Diconal and Cyclimorph). The combination product Diconal has proved particularly popular with some individuals because it also contains the opioid dipipanone. Cyclizine has been abused via the oral route in doses of 750 to 1000 mg and is reported to cause euphoria and hallucinations. Tablets may also be prepared for intravenous injection. Parenteral administration may reduce a ‘rush’ of exhilaration followed by general mental stimulation and sometimes hallucinations. The drug is more likely to be abused by those already taking opioids because cyclizine may enhance or prolong opioid effects. Of a total of 120 individuals maintained on methadone by the Trent regional addiction unit in 1989, 20 were found to be abusing intravenous cyclizine concurrently in doses of 50 to 800 mg per ‘hit’. A substantial proportion of these patients may have been cyclizine dependent; demonstrating tolerance, craving for the drug and depression or other withdrawal symptoms.

Adverse reactions to cyclizine abuse include antimuscarinic effects, tachycardia, hypertension, disorientation, mental confusion, tremor and fits. Dramatic acts of aggression, emotional lability and violent behaviour are sometimes seen. The general risks associated with tablet injection are also applicable.

Concern over cyclizine is such that it has been the subject of a statement from the Council of the Royal Pharmaceutical Society of Great Britain advising that medicines containing cyclizine should be sold personally by a pharmacist. Counsellors in drug dependency units have found the problem of cyclizine abuse to be a major challenge.

Dimenhydrinate

This is available OTC in the UK as Dramamine. High doses of the drug may cause drowsiness or exhilaration, confusion, hallucinations, antimuscarinic effects and vomiting. Dimenhydrinate  has been used by anorexic patients to decrease appetite or produce vomiting, and by those who find the sedative or psychoactive effects desirable. Doses used have varied between 600 to 3750 mg per day, and both tolerance and mild withdrawal symptoms can occur. Abuse of the related antihistamine, dipenhydramine, a drug with sedating and antimuscarinic effects, has also been reported.

Dextromethorphan

Dextromethorphan was developed as a non-opioid cough suppressant. Although similar in structure to the opioids, it does not possess typical opioid properties and probably exerts its therapeutic effect via non-opioid receptors in the central nervous system. When abused, dextromethorphan produces effects which are dissimilar to opioid intoxication. Excitation tends to occur, rather than sedation, and this is also a feature of overdose. One patient likened the experience to that of LSD. Effects that were described by 20 abusers studied by McCarthy included euphoria, hallucinations, illusions, increased perceptual awareness, hyperactivity, time distortions and synaesthesia. These actions begin within an hour of ingestion and typically last three to four hours. When abused chronically, discontinuation may bring about a withdrawal syndrome characterised by sleepiness, lethargy, depression and ataxia.

Dextromethorphan hydrobromide is usually taken orally in doses of 300 mg or more for its psychoactive effects (doses of 1500 to 2400 mg have been used). However, one case of nasal inhalation (’snorting‘) of up to 250 mg powder has been described. The main metabolite, dextrorphan, could be responsible for the psychotropic properties because it has some affinity for phencyclidine binding sites in the brain. Adverse effects from abuse may include ataxia, tachycardia, hypertension, impotence, dysphagia, diplopia. nausea, mental confusion, restlessness and irritability. Psychosis and mania have also been described.

The table below lists examples of OTC preparations containing dextromethorphan.

Opioid-containin Preparations

Opioids are dealt with in more detail in the Opioids article. OTC products containing opioids are shown in the table below.

The majority of those who abuse OTC opioids are probably established users of intravenous opioids. One study of 31 intravenous opioid abusers illustrates the reasons why OTC opioids are bought by injection drug users. In this cohort, 20 individuals had used OTC opioids; 16 used single large doses to avoid  a withdrawal reaction when intravenous opioids were not available; ten used OTC opioids in an attempt at self-detoxication; five used OTC products to supplement or augment the action of intravenous opioids. Codeine linctus was the most popular product and was named by 16 participants.

The presence of paracetamol or aspirin limits the abuse potential of OTC opioid-containing analgesics because doses needed for the purpose of abuse will tend to cause paracetamol or aspirin toxicity. Observations in Denmark suggest that some abusers are able to separate codeine from compound analgesics which also contain aspirin. However, a separation procedure developed in Glasgow using a coffee filter has been shown to be unreliable.

Abuse of codeine linctus is well known, each 100 ml comprises 300 mg of cocaine (which is equivalent to about 25 mg of morphine). Gee’s linctus contains opium tincture (equivalent to 16 mg of anhydrous morphine per 100 ml) and an extract of squill. The latter includes cardiac glycosides which have caused cardiac toxicity in heavy abusers.

Prolonged administration of kaolin and morphine mixture in large doses may cause severe hypokalaemia. Quantities such as 600 to 800 mg per day have been taken (the product only contains 7 mg of morphine per 100 ml). Hypokalaemia probably arises as a result of potasium binding by kaolin in the gut and/or from the high sodium bicarbonate content which can promote kailuresis. One case report describing a chronic user attributed death to myocardial necrosis secondary to persistent hypokalaemia and/or intestinal obstruction. Reversible hypertension may also occur in heavy users, perhaps caused by the high sodium content of the preparation.

Examples of OTC preparations containing dextromethorphan

• Actified Compond Linctus
• Contac CoughCaps
• Benylin Dry Cough
• Covonia
• Day Nurse / Night Nurse
• Robitussin Dry Cough
• Sudafed Linctus
• Tancolin
• Vicks Coldcare capsules, Medinite and certain products in this series

Examples of OTC preparations containing opioids

• Codeine Linctus
• Gee’s linctus
• Kaolin and morphine mixture
• Collis Browne’s mixture
• Dimotane Co and other branded cough mixtures containing codeine
• Codis, Panadeine, Paracodol, Paramol, Solpadeine and Veganin (compound analgesic preparations containing codeine or dihydrocodeine)

Laxatives

The majority of laxative abusers are female and the laxatives involved are almost always the stimulant variety (e.g. senna, bisacodyl or phenolphthalein). Many people who purchase OTC laxatives have constipation because of poor diet and/or lack of exercise – causes that can be easily remedied. This is unnecessary use of an OTC product, as defined in the introduction to this article. There are also patients who take laxatives when true constipation does not exist, a habit more easily defined as abuse. This practice can be very difficult to identify and there is no standard approach to diagnosis, counselling or treatment. Most abusers of this kind tend to have an associated psychiatric illness or at least a tendency towards neurosis and seem to fall into two groups: those with eating disorders and those with bowel obsession.

Eating disorders

Patients with bulimia or anorexia nervosa may abuse laxatives; one review suggested that bulimia patients may be more than three and a half times more likely to abuse laxatives than the general population. Most sufferers are women between late teenage and 30 years of age. They may believe that laxatives will reduce the calorific impact of food by reducing absorption and thus preventing weight gain, although this is obviously not the case. Some ill-informed members of the public who do not suffer from eating disorders may also use laxatives in this way as an aid to dieting. Laxatives might reduce the subjective feelings of ‘bloatedness’ that many bulimia patients find upsetting or diminish any abdominal cramping. Interestingly, studies suggest that laxative abuse by bulimics may cause an increase in anxiety that dissipates once abuse is discontinued.

Bowel obsession

These patients tend to be older than those in the previous group and often have one of a number of associated mental disorders (e.g. depression, dementia, anxiety, various neuroses). There may be an obsession to defaecate regularly at the same time of the day and/or to produce stools of a certain precise appearance. These beliefs may have arisen from training instilled in childhood, from a previous experience of constipation or from a belief that regular bowel habit is necessary for bodily cleanliness. Some may have suffered from real constipation initially but persistent abuse of stimulant laxatives causes a degree of tolerance to their effects and consequently dosage tends to be progressively increased.

Not surprisingly, many laxative abusers suffer from chronic diarrhoea which may result in electrolyte disturbances related to malabsorption and its sequelae. Sodium and water loss encourage hypokalaemia, which is quite common; hypocalcaemia and hypomagnesaemia can also occur. Electrolyte derangement can result in acute renal failure and steatorrhoea has been reported rarely.

Long-term use of stimulant laxatives is likely to result in atonic colon characterised by loss of normal colonic mucosa structure. This in turn causes intractable constipation, a physical inability to defaecate and periodic faecal impaction. Such patients often fail to respond at all to stimulant laxatives and bowel cleansing solutions may be the only treatment option.

Simple Analgesics

OTC analgesia is often used unnecessarily. In one survey in the 1960s, 40 per cent of interviewees who took OTC aspirin for medicinal purposes did so for indications where aspirin has no therapeutic benefit. However, abuse, as defined in this article, is rare. It is sometimes claimed that ingestion of a mixture of one or two soluble aspirin with a fizzy cola drink or beer will produce a ‘high’. There is no evidence that this is anything other than a placebo effect.

Nonetheless, some people appear to derive pleasurable intoxicating effects from dangerously high doses of aspirin. Two cases have been described by Madden and Wilson. In one of these, 20 to 30 aspirin 300 mg tablets were taken which ‘produced an agreeable haze, with a disembodied feeling of detachment accentuated by deafness; tinnitus was a ‘gentle singing noise, very soothing’. Salicylism produced a condition of ‘isolation, relaxation, protection’.‘ Abuse of an aspirin / caffeine preparation was held to be responsible for deterioration in seizure control and violent outbursts in an epileptic who took the equivalent of 13 g aspirin and 2 g caffeine per day. Dependence of the aspirin-type has been defined and claimed to meet the World Health Organization criteria for drug dependence.

Paracetamol abuse was described in four female patients with eating disorders. In each case, overdoses of paracetamol between eight and 30 tablets (500 mg) were taken to induce vomiting after food binges or when subject felt overweight. Clearly, large doses or aspirin or paracetamol, as described here for the purpose of abuse, carry the potential for a fatal outcome.

Miscellaneous

Alcohol

Some preparations contain ethanol in high concentration (e.g. surgical spirit, methylated spirits, aftershave) and may be purchased by alcoholics.

Anabolic compounds

A range of products that are available OTC are claimed to have anabolic properties. These include arginine, ornithine, carnitine and inosine. However, in most cases these claims are founded on poor quality evidence (see Performance Enhancing Drugs).

Antimuscarinics

Antimuscarinic abuse has already been discussed (see Prescription Drugs) but it should be noted that Kwells, an OTC travel-sickness remedy, contains an appreciable quantity of hyoscine.

Aromatic amines

A toxic psychosis developed in a patient dependent on mentholated cigarettes. Psychiatric symptoms returned when she was exposed to pure menthol. A second patient discovered that Vicks Vaporub and Sinex nasal spray gave her ‘a pleasant psychological lift’ when applied intranasally throughout the day. Although the spray contains oxymetazoline, a sympathomimetic, both spray and rub contain large amounts of camphor and menthol. Certain Vicks products are also used by those taking ecstasy to help smooth the aftermath of a ‘trip’.

Caffeine

Caffeine-containing preparations such as Pro-Plus and Labiton are sold OTC for their stimulant effects. Although no more effective than caffeinated beverages, some members of the public are undoubtedly attracted by the ‘medicine-like’ format. Large doses have been taken for the purpose of abuse.

Illicit drug manufacture

Table below lists some chemicals which may be used in order to manufacture drugs of abuse.

Chemicals used in clandestine production of drugs.

Chemical	Substance produced
Acetic anhydride	Heroin, methaqualone
Acetone	Cocaine, heroin, others
Ammonia	Cocaine
Ammonium chloride	Heroin
Ammonium hydroxide	Cocaine, others
Anthranilic acid	Methaqualone
Benzaldehyde	Amphetamines
Benzyl cyanide	Methamphetamine
2-Butanone (MEK)	Cocaine
Chloroform	Cocaine, others
Diethylamine	LSD
Ephedrine	Methamphetamine
Ergometrine	LSD
Ergotamine	LSD
Ethyl ether	Cocaine, heroin, others
Hydrochloric acid	Cocaine, heroin, others
Isosafrole	Ecstasy, MDA, MDE, etc.
Lysergic acid	LSD
Methylamine	Methamphetamine, ecstasy
3,4-Methylenedioxyphenyl-2-propanone	Ecstasy, MDA, MDE, etc.
Methyl isobutyl ketone (MIBK)	Cocaine
N-Acetylanthranilic acid	Methaqualone
Nitroethane	Amphetamines
Phenyl-2-propanone	Amphetamine, methamphetamine
Piperidine	Phencyclidine
Piperonal	Ecstasy, MDE, etc.
Potassium carbonate	Cocaine
Potassium hydroxide	Cocaine
Potassium permanganate	Cocaine
Propionic anhydride	Fentanyl analogues
Pseudoephredine	Methamphetamine
Pyridine	Heroin
Safrole	Ecstasy, MDA, MDE, etc.
Sodium carbonate	Cocaine, others
Sodium hydroxide	Cocaine, others
Sulphuric acid	Cocaine, others
Tartaric acid	Heroin
Reproduced from the Centre for Pharmacy Postgraduate Education distance learning pack ‘The treatment of drug dependence’.

Weak acids

Absorbic or citric acids may sometimes be used to convert street heroin into a more water-soluble form for injection.

Controlling The Problem

Most community pharmacists are aware of the fact that abuse of OTC medicines occurs. However, it is difficult to know what can be done to prevent the problem or how best to help those that are affected. A valuable counselling service for affected patients (’Overcount’) has been established but has no direct input from healthcare professionals. Printing warnings on medicines which state that the product may be liable to abuse or can cause dependence may alert some users to the dangers but will also serve to attract others to ‘experiment’ with them. By analogy, warnings on cigarettes seem to be a minimal deterrent. Restricting all potentially abusable products are used to treat minor ailments such as colds, diarrhoea and coughs. The prospect of visiting a busy GP every time a supply of such medicine is required, and paying a prescription charge which far exceeds the cost of the medicine, would meet resistance from GPs and the public alike. In addition, as Prescription Drugs article makes clear, prescription only status is certainly no guarantee against abuse and dependence.

There is a course of action which is more likely to be effective in reducing OTC abuse. Unfortunately, it would be time-consuming to operate and some might take the view that the inconvenience it would impose on so many is far too great compared to the relatively small scale of OTC drug abuse. The situation is also complicated by the fact that patterns of OTC medicine abuse are constantly changing. The course of action is outlined below.

• Continue to educate all community pharmacists concerning which products are liable to abuse and continue to strike from the register those found guilty of supplying OTCs with the knowledge that they will be abused.
• Recognise nationally the existence of OTC drug abuse and establish treatment guidelines for the various forms of abuse.
• Restrict cyclizine to ‘prescription only’ status because there are non-abusable alternatives available OTC.
• Reformulate all OTC cough and cold mixtures which contain dextromethorphan or sympathomimetic so that these constituents are removed. The evidence for efficacy of these cocktail products is extremely limited and any benefits produced are small. The British National Formulary has acknowledged this fact for many years.
• Educate the public that most cough and cold treatments will at best provide only a temporary relief of symptoms and that they will not alter the course of the condition.
• Remove the morphine from Gee’s linctus, kaolin and morphine, and similar products because there is little evidence that the opioid constituents are necessary.
• The main abusable cough/cold preparations available OTC would then be pseudoephredine tablets and codeine linctus. Pharmacies should keep registers for sales of these products to members of the public, who would need to produce evidence of identity before a sale. A similar regulation might apply to laxative abusers.
• The names of regular purchasers should be exchanged by local pharmacies, and patients with an identified problem should be referred to drug dependency units. Further supply to these patients should be withheld. Laxative abusers could be referred to a GP and then if necessary to a gastroenterologist or psychiatrist.

Are You Addicted To Over-the-counter Products?

If you are addicted to over-the-counter products or any other drugs mentioned in this article, there is help available. The Causeway Retreat specializes in the treatment of addiction problems. All you need to do is calling us on 0207 100 7260 or contacting us by using the form below. All of the information you supply to us about yourself remain confidential. Call us now: 0207 100 7260.