This article has been taken from a MSc module initially written by Dr Brian Jenkins, Senior Lecturer in Anaesthetics and Intensive Care and Honorary Consultant Anaesthetist, Department of Anaesthetics, Intensive Care and Pain Medicine, Cardiff University and has subsequently been updated and expanded by Dr Sarah Fox. Sarah is currently working in Psychiatry of Older Adults, and she continue her longstanding interest in pain management (Sarah previously worked in a pain clinic and then Bath Centre for Pain Services).
Sarah is involved in a project with Bristol PCT, called PAIN (Pain Assessment in Nursing homes) looking at more effective management of pain in people with dementia. She also has an interest in pain and depression/anxiety disorders in patients of all ages. Through her own personal experience and her ongoing work with support groups for patients with chronic pain around the world, she has interests in iatrogenic conditions and medically unexplained symptoms.
This article discusses the substances that can be misused including the legal drugs such as alcohol and tobacco, misuse of the prescription drugs and illegal drugs.
This section discusses recreational drugs that are legal within the UK. By far and away the biggest problems in terms of health result from the recreational use of alcohol-containing drinks and tobacco smoking.
Currently, in the UK, alcohol use is extremely popular and common. It is used experimentally by adolescents, recreationally by adults, and in some individuals involves a psychological and/or physical dependence.The latter group presents a major public health challenge. Problems occur when ingestion becomes excessive, or from addiction to the effects of alcohol.
Excessive alcohol intake is common in all social groups, and increasingly in young adults who indulge in ‘binge drinking’ due to easy access to cheap often sugary drinks. It is a common reason for hospital admission. Alcohol ingestion commonly precedes admission for trauma and other injury.
Due to the effects on the frontal lobe of the brain, alcohol intoxication causes disinhibition which is expressed in heightened aggression and sometimes sexuality. Therefore alcohol is often associated with crimes related to this, including Saturday night brawling in pubs and domestic violence.
For more information on alcoholic liver disease and the questions patients may ask you click on the following video.
Heavy drinkers can also suffer from hypertension  cardiomyopathy and heart failure, memory , thyroid dysfunction , changes in gait, tremor, and nystagmus. In fact, alcohol can affect every part of the body adversely. It is associated with an increased risk of certain types of cancer.
Using the current Office of National Statistics (ONS) definition, there were 6,769 deaths in England in 2008 that were directly related to alcohol. The most common cause of death linked to alcohol consumption was alcoholic liver disease (Office of National Statistics 2010).
Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning, which are thought to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. These repeated periods of acute intoxication followed by acute detoxification are also associated with an increased risk of seizures.
The alcohol withdrawal syndrome can vary in severity from mild symptoms (sleep disturbances and mild anxiety) to very severe and life threatening including delirium, with visual hallucinations and convulsions which may lead to death.
The severity of alcohol withdrawal depends on various factors including age, genetics, and, in particular the level of alcohol intake and length of time the individual has been misusing alcohol as well as the number of previous detoxifications. Kindling is the phenomenon where repeated alcohol detoxifications lead to an increased severity of the withdrawal syndrome. Kindling is associated with a higher risk of complications including brain damage, cognitive deficits as well as risk of relapse.
There may also be a protracted withdrawal syndrome that persists for months after stopping alcohol.
Alcohol withdrawal tends to start within 48 hours of last alcohol intake. It requires careful medical management to avoid neurological damage.
In terms of its direct effect on health, tobacco smoking is undoubtedly the most damaging recreational drug. Its effects on the health economy are only rivalled by alcohol-related morbidity and mortality. Research has estimated that smoking cost the NHS in the UK £5.2 billion in 2005/06, approximately 5.5% of total healthcare costs. In 2007/08 there were 1.4 million NHS hospital admissions amongst adults aged 35 and over for diseases that can be caused by smoking. In 2008, 83,900 (18%) of deaths of adults aged 35 and over in England were estimated to be attributable to smoking (ONS 2009).
Cigarette smoking produces an increased heart rate respiratory rate, blood pressure and arrythmias  due to the effects of the nicotine and the ‘enhancers’ most commercially available cigarettes contain (which aim to give the smoker a more rapid ‘hit’). It reduces the oxygen carrying capacity of blood, and has a wide variety of long term effects including increased risk of cancer of various types, ischaemic heart disease, chronic pulmonary disease, peripheral vascular disease, and even dementia. If the smoker is pregnant there can be serious effects on the foetus.
Tobacco smoking is also implicated as a ‘gateway drug’, i.e. one which leads on to other substance misuse e.g. cannabis smoking.
Misuse of prescription drugs
Prescription drugs may be misused by the person they are prescribed for (excess doses taken) or diverted to other users purely for recreational use.
Chronic pain is a common problem. Studies show that in recent years there has been an increasing use of prescription opioids for non-cancerous chronic pain and concomitantly a marked increase in abuse of prescribed opioids between 1997 and 2002 . Reports of the rate of opioid abuse in patients receiving chronic-pain management range from 9% to 41 % .
UK statistics showed over 2000 deaths related to analgesic and cough-suppressant opioids in England and Wales from 1996-2002 . The more recent TROUP study in the US looked at trends in use of opioids for non-cancer conditions confirmed continuing rises in opioid prescription from 2000-2005 . Around 3% of users of chronic opioid therapy had an abuse/dependence diagnosis, there was an inverse relationship between age and a diagnosis and there was an association with mental health and substance use disorders .
Even over the counter analgesics are associated with significant morbidity .
Some opioid misuse comes from surprising and innovative sources: e.g. chewing a Fentanyl patch  or dissolving the patch and injecting it.
In addition to opioid misuse, there may be benzodiazepine misuse as these drugs can be prescribed for pain-related anxiety or for muscle relaxation.
It is not feasible to provide an exhaustive list of abused substances. Routes of administration are also many and varied. Illicit drugs can be taken orally, injected intravenously, intramuscularly, inhaled, applied topically, exactly as legal and medical drugs.
For a drug to be injected, it must obviously be in liquid form, but most illegal drugs are sold as solids. Typical forms are tablets, powders, or in some cases the dried unprocessed plant.
Illegal substances distributed as powder almost always include other substances in order to increase bulk, stabilise the active agent and maximise profits. Virtually all they have in common is that they are (relatively) inert, cheap and readily available.
In order to be injected intravenously, drugs obtained as tablets or powders are commonly dissolved in water or some other solvent before injection. Unfortunately, many adulterants (such as talcum powder) are not readily soluble in water, attempts to do so produce a suspension that is then injected intravenously. Substances that can only incompletely dissolve may embolise following injection and cause infarction of tissues or organs.
Worldwide, the United Nations estimates there are more than 50 million regular users of heroin, cocaine and synthetic drugs. Global users of heroin are estimated at between 15.16 million and 21.13 million people aged 15–64. The largest producer of opiates in the world is Afghanistan, which produces 93% of the world’s market.
Of the estimated 4 million people in the UK who use illicit drugs each year (by far the most commonly used being cannabis), approximately 50,000 people misuse opioids, although this may be an underestimate. Furthermore, opioid misuse is associated with much greater rates of harm than misuse of either cannabis or cocaine. Over 150,000 people are in treatment for opioid misuse and are prescribed opioids such as methadone and buprenorphine.
Morphine from the opium poppy has been used for thousands of years. In the 16th Century, Paracelsus discovered the properties of tincture of opium. He called this laudanum, and a similar concoction was made by Thomas Sydenham in the 1660s which was taken as laudanum which contained 10% opium (about equivalent to 1% morphine). It contained a variety of other substances, often spices and alcohol. It was used for many purposes including pain relief, sedative/hypnotic, anti-diarrhoeal, anti-tussive. Laudanum was available without prescription until the early 20th Century and was present in many patent medicines. To this day it is still manufactured both in the UK and abroad but is rarely prescribed.
Opioids can be divided into 3 classes:
Naturally occurring opioids: opium and morphine. Opium is extracted from Papaversomniferum (the opium poppy), and morphine is the primary active component of opium. Endogenous neural polypeptides such and endorphins and enkephalins are also natural opioids.
Semi-synthetic opioids: (chemical synthesis using compounds isolated from natural sources) include heroin, oxycodone, oxymorphone, and hydrocodone.
Synthetic opioids: made using total synthesis, from petrochemicals: buprenorphine, methadone, fentanyl, alfentanil, levorphanol, meperidine, codeine, and propoxyphene.
Endogenous peptides regulate and modulate several important functions. The majority of opioids have effects on µreceptors with the following physiological effects:
Mood alteration (often producing euphoria and decreased anxiety)
Respiratory depression (can cause death in overdose)
Decreased gastrointestinal motility (can cause constipation)
Suppression of corticotropin-releasing factor and adrenocorticotropin hormone
Pinpoint pupils (miosis)
Nausea, vomiting, pruritis (less common), etc
Morphine is known on the street and elsewhere by a wide variety of names including M, Emma. Lady M, white lady, dope, needle candy. MS Contin tablets are known as misties, and the 100 mg extended-release tablets as greys and blockbusters. Oxycontin is also known in the US as hillbilly heroin.
Diamorphine (Heroin) is the most commonly abused substance, but many other opioids are also available including synthetic opioids predominantly used in hospitals; resale (‘diversion’) of prescription-only analgesics is a common source.
Misuse of morphine typically involves taking higher doses than prescribed or outside of medical supervision, injecting oral preparations, mixing it with unapproved potentiators such as alcohol, cocaine, and/or circumventing the extended-release mechanism by chewing the tablets or turning into a powder for snorting or preparing injectables. Morphine is generally difficult to divert and is therefore uncommon on the street, although ampoules and phials of morphine injection, pure pharmaceutical morphine powder, and soluble multi-purpose tablets are very popular where available. Taken orally the drug is subject a first pass metabolism, which is why intravenous injection is preferred.
Mortality and Morbidity
Mortality, particularly in heroin-dependent users, is high, around 10-20 times that of the
general population. In England and Wales, there were 1,382 drug-related deaths in 2005 (National Programme on Substance Abuse Deaths, 2005). The majority (59%) were cases of accidental poisoning, although a significant proportion (16%) was a result of intentional self-poisoning. Opioids (alone or in combination with other drugs) accounted for some 70% of the deaths, and cocaine 13%. Many of the deaths appear to be due to multiple drug toxicity, especially the presence of central nervous system depressants (for example, alcohol and benzodiazepines), rather than simply an ‘overdose’ of an opioid.
Repeated injection will have medical consequences, such as scarring, infection of blood vessels, abscesses, and compromised functioning of the kidney, liver and lungs (with increased vulnerability to infections). HIV infection is a major problem for injecting drug users, with the number of new diagnoses of HIV in the UK holding at around a hundred for the last few years, around 5% of all UK diagnoses being attributed to injecting drug use. Rates are higher in some centres such as London. Approximately 50% of injecting drug users have been infected with hepatitis C.
Transmission of both hepatitis A and B continues, even though there are effective vaccines. Needle and syringe sharing increased in the late 1990s and since then has been stable, with around one in three injecting drug users reporting this activity in the last month.
Effects on general health
Long term use can result in demotivation, depression, difficulty concentrating, sleep disturbance and sexual problems.
Constipation is a common and sometimes serious problem.
Appetite may be reduced, resulting in malnutrition
Large doses may cause agitation, tremors.
Chronic use may affect the immune system
Symptoms of withdrawal from opioids (‘cold turkey’) can range from mild (some anxiety, sleeplessness, drug craving, ‘flu like feeling) to moderate (nausea, cramping, diarrhoea, tremors, insomnia) to severe (agitation and pain, kicking legs, elevated temperature).
The main effects of cerebral stimulants are to elevate mood, decrease tiredness and promote increased activity. This stimulation usually comes at a price, with a spell of tiredness following the stimulation.
Use in high doses may lead to anxiety, tremors, sleep disturbance and exhaustion. These drugs are particularly dangerous in individuals with cardiovascular pathology such as angina, where increased cardiac workload may result in acute infarction. The main abused illegal stimulants are cocaine, amphetamine, amphetamine derivatives and the so-called hallucinogenic amphetamines such as MDA and MDMA.
For over a thousand years, indigenous South Americans have chewed the leaves of the coca plant which contains alkaloids including cocaine. Remains of coca leaves have been found with ancient Peruvian mummies, and pottery from the time period depicts humans with bulged cheeks; it is thought a combination of coca and saliva was used as an anaesthetic when trepanning was performed.
In Western societies, cocaine has increased in popularity in recent years, being associated with abuse among affluent classes. South America remains the major source of cocaine to the present day.
Cocaine has been and is still used medically as a local anaesthetic. Initially it was used in the eye and then for spinal anaesthesia in the late 19th Century. The original recipe for Coca Cola in 1886 contained cocaine.
Sigmund Freud, inhis work Über Coca, wrote that cocaine causes
“exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person…You perceive an increase of self-control and possess more vitality and capacity for work….In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug….Long intensive physical work is performed without any fatigue…This result is enjoyed without any of the unpleasant after-effects that follow exhilaration brought about by alcohol….Absolutely no craving for the further use of cocaine appears after the first, or even after repeated taking of the drug…”
There are basically two forms of the abused drug; cocaine hydrochloride and free-base cocaine.
Cocaine hydrochloride is a white powdery solid that can be dissolved in water and injected, or it may be ‘snorted’ as the powder. The practice of snorting (‘tooting’ through a variety of devices including rolled up bank notes) is particularly popular, and produces an immediate adrenaline rush when the drug is rapidly absorbed into the blood via the nasal capillaries. Long-term use in this fashion can lead to damage to the nasal septum and mucosa secondary to the vasoconstrictor effects of cocaine, producing ischaemia and eventual loss of nasal cartilages.
Free-base cocaine is a crystalline solid that is commonly produced by combining cocaine hydrochloride with water and sodium bicarbonate and evaporating excess water from the resulting solution. The resulting compound is not in-activated by heat (unlike the hydrochloride), and so is able to be smoked with preservation of the active ingredient. ‘Crack’ is a common nickname for free-base cocaine which describes the sound made when the compound is heated during smoking. It has become notorious in recent years as a highly addictive but relatively cheap variant of cocaine.
To watch a video on two peoples experience of cocaine addiction click here.
The main action of cocaine is to block the re-uptake of catecholamines at peripheral and central sympathetic receptors, thus increasing the duration and effect of catecholamines at these receptors. The main central effects are euphoria, a feeling of well-being and tirelessness. In higher doses agitation, panic attacks and tremors are seen. Convulsions have also been reported, particularly in association with over-activity and hyperthermia. Chronic and heavy users may develop hallucinations that take many forms. Tactile hallucinations resembling small animals crawling across the skin are well described, but visual hallucinations ‘snow lights’ and auditory hallucinations may also occur. Paranoid ideation and schizophrenia-like states have also been reported.
The main peripheral effects are tachycardia, hypertension and an increased incidence of dysrhythmias. Cocaine increases myocardial oxygen consumption and work. It may also be responsible for coronary artery spasm, thus increasing demand for oxygenated blood in situations where the normal delivery mechanisms are impaired. Profound peripheral vasoconstriction may provide conditions that precipitate acute heart failure is precipitated, but this may also occur as a result of ischaemia, dysrhythmias or tachycardia. Acute pulmonary oedema has been reported, as has cardiomyopathy.
Smoking of free-base is usually associated with a valsalva-like manoeuvre that maximises absorption of cocaine via the lung. This practice has been associated with pneumothorax and pneumomediastinum, presumably as a result of prolonged high intra-alveolar pressures.
Intravenous cocaine causes ringing in the ears moments after injection (usually when in excess of 120 milligrams) lasting 2 to 5 minutes (known as a ‘bell ringer’).
Amphetamines are a very commonly abused class of cerebral stimulants, probably due to relative low cost and a widespread belief that there are few side effects associated with their use. They tend to have a reputation as ‘poor-man’s cocaine’, and they produce similar effects to cocaine following acute intake.
Amphetamines have a direct stimulant effect at sympathetic receptors; they also increase release of catecholamines from nerve-endings and prevent re-uptake in a manner similar to cocaine.
Like cocaine, the mainly positive central effects of amphetamines are euphoria, increased alertness and tirelessness. They have been taken as performance-enhancing drugs by athletes and those who would like to be regarded as sexual athletes. Hallucinations may also occur following acute intake, but these are generally regarded as unpleasant by most users.
In order to reduce the incidence of hallucinations, benzodiazepines or barbiturates may be taken with the amphetamine. These combinations tend to accentuate and prolong the euphoric effects of the stimulant whilst reducing withdrawal symptoms. In high doses, and/or with chronic use, psychiatric side effects become more prominent, with paranoid psychoses, hallucinations and delirium becoming more common. If the habit is not detected, a diagnosis of acute schizophrenia may be made following an acute psychotic episode.
Peripheral effects include hypertension, tachycardia and tremulousness. Hyper-activity, hyperthermia and muscular spasms occur in higher doses, along with convulsions and delirium. Effects are longer-lasting than following cocaine ingestion, typically lasting several hours following intake.
Tolerance to high doses is seen in chronic use, and initial euphoria following intake seems to be replaced by chronic depression as the amount of drug consumed falls behind the dose required to prevent withdrawal symptoms. Chronic use is associated with loss of receptors in those areas of the brain that are stimulated by amphetamines, producing long-term neurological damage that may help to explain psychiatric symptoms that persist long after the drug can be detected in the body.
MDMA is a very common drug of abuse in the UK, and in recent years has achieved a considerable degree of notoriety in the press under it’s street name ‘Ecstasy’. Death has been reported in first time ecstasy use, and there is an increasing number of admissions to accident and emergency departments . Nevertheless, it is estimated that 500,000 people take ecstasy in the UK every weekend, with 96% of clubbers admitting to trying the drug (Winstock et al 2001).
MDMA produces a number of positive mood changes, inducing euphoria, increased sociability and tirelessness. Side effects include decreased appetite, palpitations, muscle spasms, insomnia, memory impairment (, ) and panic attacks. Some of the more severe neurological side effects of peripheral sympathetic stimulation, such as intracerebral haemorrhage , sub-arachnoid haemorrhage , and cerebral infarction have also been reported.
The main effects of MDMA seem to be on serotonin release and metabolism. However, with long-term use, evidence from animal experimentation suggests that MDMA acts as a neurotoxin on serotonergic neural pathways, producing a decrease in serotonin levels that may last for months .
Typically, individuals present following a period of prolonged activity ending in unconsciousness, sometimes preceded by seizures. On admission to hospital, they are hypertensive and tachycardic, and sweat profusely. They have dilated pupils, raised temperature (typically greater than 39.5°C), and muscular rigidity. High temperature and sustained muscle contractions may lead to rhabdomyolysis, acidosis, multiple organ failure and death.
The reason why a hyperthermic syndrome occurs following prolonged activity in some individuals but not others is unclear. Dehydration may be one important factor directly relating to features such as acidosis and shock, but other factors such as genetic predisposition may play a part, as in heat stroke .
O’Regan & Clow  found that MDMA, in the short term, may cause serotonin-mediated alterations in pain sensitivity, with reduced pain tolerance.
Animal experiments indicate that both moderate and high dose or rapidly repeated MDMA exposure may lead to dose-dependent long-lasting serotonergic changes likely to be due to neurotoxicity. Also, rat studies suggest environments or activities that increase the animals’ body temperature increase serotonergic changes. PET and SPECT studies in humans have found reduced levels of serotonin transporter in recently abstinent MDMA users as well as evidence of partial or full recovery with prolonged abstinence but a recent review  stated that no conclusions could be drawn at that time.
MDMA use has been found to be associated with impairments of psychological well-being, verbal memory and altered serotonergic functioning in a number of cross-sectional studies but there have been inherent methodological limitations, particularly the notorious polydrug use of ecstasy users. Thomasius et al  found that verbal memory showed no sign of improvement even after prolonged abstinence which may represent persistent functional consequences of MDMA neurotoxicity.
There have also been studies  suggesting a slight tendency to be more impulsive and have lower mood. A more recent study  suggests that previous reports of marked subacute effects of ecstasy use may have been confounded by chronic polydrug use before current use, co-substance use and sleep disturbances after use.
As the name suggests, drugs in this section are used to promote sleep or sedation. Hypnosedatives are generally referred to by abusers as ‘downers’, describing their main effects on mood and activity.
They are commonly used in combination with certain ‘uppers’ (or cerebral stimulants) in order to control the anxiety and panic reactions commonly seen, or to simply promote sleep following stimulant ingestion.
Benzodiazepines now dominate the choice of hypnotic sedatives in most situations, almost completely replacing the more toxic barbiturates. Before benzodiazepines were developed, the problems associated with barbiturates were well-known. Between the barbiturates and benzodiazepines, other classes of drugs were developed and used in an attempt improve on the safety profile of the barbiturates.
The main action of benzodiazepines is in the central nervous system, having an effect similar to the naturally-occurring neurotransmitter gamma-amino butyric acid (GABA).
Following intake, there is a feeling of calm, with sedation and hypnosis in larger doses. Respiratory depression may be present, though it is not usually life-threatening following benzodiazepine intake alone. However, other cerebral depressants such as alcohol and barbiturates may have a synergistic effect on respiratory depression, precipitating life-threatening respiratory depression. Hypotension is another frequent physiological effect.
In low doses they may have useful anxiolytic effects, and are frequently used in hospitals as premedications for minor surgical and endoscopic procedures. Some side effects of the benzodiazepines such as antegrade memory loss may be beneficial during unpleasant procedures such as fracture reduction, but can cause anxiety if not explained to the patient.
This effect has led to the illegal use of some of these drugs such as midazolam and triazolam in so-called `date-rape’ scenarios. With chronic use over 4 weeks, tolerance to the effects of benzodiazepines may develop, resulting in an increase in the dose required to produce a desirable effect.
Temazepam initially achieved popularity as short-acting hypnotic, particularly for elderly patients, where older, longer-acting benzodiazepines were known to produce damaging hangover effects. In order to produce a more euphoric effect, abusers aspirated the liquid contents from the gel capsules, creating a highly potent injectable preparation.
This practice was cheap for dealers, highly addictive for users, and became very popular in the UK. The Home Office responded by asking the manufacturers to change the drug formulation in order to eliminate this practice. They responded by producing ‘abuse-resistant’ capsules in which the active agent was combined with a waxy substance, effectively solidifying the capsule contents. Unfortunately, this did not solve the problem, and actually made things far worse. The drug could still be injected by heating the capsule in hot water; this melted the contents, which could then be injected intravenously.
Following injection into veins, the drug tended to re-solidify, causing venous obstruction, tissue ischaemia and gangrene . Muscle infarction, rhabdomyolysis and myoglobinuria has also been reported, sometimes being associated with acute renal dysfunction.
Withdrawal from benzodiazepines
Unlike opiate withdrawal which is unpleasant but not life-threatening, withdrawal from ‘Benzos’ can be dangerous, the main concern being the onset of seizures. Note in particular that extreme sensory sensitivity and pain can be a consequence of withdrawal.
Psychological symptoms – such as anxiety, depression, panic attacks, odd sensations, nightmares, feeling as if you are outside your body, feelings of unreality, or just feeling awful. Rarely, psychosis
Physical symptoms such as sweating, being unable to sleep, headache, tremor, feeling sick, feeling unsteady, palpitations, muscle spasms, and being oversensitive to light, sound and touch. Rarely, convulsions (seizures) occur.
In some cases the withdrawal symptoms seem like the original anxiety symptoms.
Withdrawal symptoms may persist for weeks to months, depending on the speed of the withdrawal and which drug was stopped. Some doctors advocate switching from other benzos to an equivalent dose of diazepam and then following a slow tapering regimen over a period of weeks to minimise withdrawal effects.
Benzodiazepine dependence and withdrawal has been associated with suicide and self harming behaviors, especially in young people. The Department of Health substance misuse guidelines recommend monitoring for mood disorder in those who are dependent on or withdrawing from benzodiazepines .
Parts of the hemp plant have been smoked and ingested for over two thousand years. In more recent times, cannabis elixir was in fact available on prescription in the UK until the 1950s. Cannabis is listed in the 1929-1930 Physicians’ Catalog of the Pharmaceutical and Biological Products of Parke, Davis & Company as an active ingredient in ten products, combined with other substances such as morphine, used for sedative and analgesic effects or codeine, as a cough suppressant.
Nowadays, cannabis preparations may take many different forms, depending on the part of the plant used and how it is processed. The leaves may be dried and smoked as marijuana or ‘grass’. Cannabis resin is the form most commonly available, and is usually mixed in small quantities with tobacco and smoked.
Cannabis preparations contain a large number of active agents, but the tetrahydrocannibinols are thought to be the main constituents responsible for the well-known effects following intake. Different types of cannabis have varying strengths of tetracannabinol (THC). For instance, the leaves have a lower concentration than the resin. Certain types such as ‘Northern Lights’ and ‘skunk’ bought on the street have higher levels of THC. Patients with chronic pain may use cannabis in an attempt to control pain and its associated emotional distress. They may not be aware of the dangers in where they source their drugs.
Inhalation of marijuana smoke is more harmful than tobacco smoke; cannabis smoke delivers 50% to 70% more carcinogens. Other physiological effects include decreased immune function, higher rates of cardiac arrhythmias, and documented cases of cerebellar infarction. Marijuana may exacerbate depression and anxiety (including panic attacks), as well as causing memory problems that may persist for a month after last use. Cannabis abuse is a risk factor for psychosis in genetically predisposed people and may lead to a worse outcome of schizophrenia.
Symptoms following ingestion include mild sedation and relaxation, distortion of time and a general feeling of warmth and well-being . Around 1 in 10 cannabis users have unpleasant experiences, including confusion, hallucinations, anxiety and paranoia. The same person may have either pleasant or unpleasant effects depending on their mood and circumstances at the time of taking the drug. These feelings are usually only temporary, but may last longer than the user expects because the drug can stay in the system for some weeks. Long-term use can have a depressant effect, reducing motivation.
Cannabis may also interfere with a person’s capacity to concentrate, organise and use information, which may last several weeks after use, and can cause particular problems for students.
Like LSD, autonomic effects are evident, with tachycardia and hypertension being common. Miosis and engorgement of the corneal capillaries are typical and may be useful sign of recent ingestion. Effects on the CNS are complex, with elevation of both serotonin and acetylcholine levels in the brain.
Withdrawal symptoms have been shown in heavy users and include:
- decreased appetite
- sleep difficulty
- weight loss
- aggression and/or anger
- strange dreams
Cannabis preparations have been used to treat certain types of pain, such as that associated with multiple sclerosis and arthritis. Hard evidence for its efficacy in this regard is lacking, and research examining the analgesic effects of cannabis is currently being sponsored, with synthetic preparations being tried for neuropathic pain. The anti-emetic effects of tetrahydrocannibinols are well known.
Commercial preparations of cannabinoids exist for the treatment of severe nausea and vomiting, particularly that associated with chemotherapy and high doses of opiates in palliative care. A synthetic version of THC is available in capsule form as the prescription drug dronabinol (Marinol) in many countries. Sativex, an extract of cannabis administered as a sublingual spray, has been approved in Canada for the treatment of multiple sclerosis.
Hallucinogenics achieved their most widespread popularity in the 1960s, but their use also increased in the 1980s and 1990s in association with ‘rave’ culture. Most individuals find their main effects disturbing and unpleasant, and they have never been as popular as some other classes of drugs. Lysergic Acid Diethylamide (LSD) is the drug most commonly associated with this group, although many others are also used, and many other classes of abused drugs are capable of producing hallucinogenic side effects.
Other hallucinogenic drugs such as ketamine and phencyclidine occasionally become popular, particularly when other drugs are in short supply, but like LSD, most drug abusers find their effects too disturbing for regular use.
The LSD molecule has similarities to serotonin, and its main hallucinogenic actions are thought to occur as a result of inhibition of the effect of serotonin within the CNS. However, both agonist and antagonistic effects have been reported, and the result is a complex and poorly understood effect.
LSD was synthesised in 1938 by a Swiss chemist and the psychedelic properties discovered in 1943. Early medical uses included during psychotherapy to aid disinhibition and access to the unconscious mind. During the 1950s and 1960s hundreds of Psychiatrists worldwide used LSD with positive results ; there was even a specialist LSD unit in the UK.
LSD was studied in the 1960s  as an analgesic for severe cancer or trauma-related pain. Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates as well as more lasting in its benefit (providing some pain reduction for as long as a week after peak effects had subsided). The effect was attributed to a decrease in anxiety and distress due to pain. There are ongoing studies into this benefit in terminal cancer patients and recent studies in LSD to treat cluster headaches .
LSD is well absorbed orally, and is usually sold with the drug adsorbed onto a porous substance such as blotting paper, which is then cut into squares, or tabs, they may then be swallowed or infused in a drink. Following oral ingestion, hallucinations commence in 1-2 hours and are generally quite prolonged, with duration of action from 8-12 hours.
LSD hallucinations are typified by changes in normal perception and mood, producing distortion of body self-image, and vivid visual and auditory hallucinations. Acute depersonalisation occurs, sometimes with acute anxiety and panic attacks. Paranoid ideation resembling schizophrenic symptoms have also been reported, so that hallucinogenic abuse should always be considered as a differential diagnosis in any situation where schizophrenia is newly diagnosed.
There are also consistent peripheral effects, such as increase in muscle tone and hyperreflexia. An increase in sympathetic tone is also usual, resulting in elevated blood pressure, tachycardia, mydriasis and piloerection. Hypothermia has been described, so that accurate measurements of temperature may be required in patient management following acute ingestion.
LSD may cause ‘flashbacks’ some time after the actual ingestion of the drug, and these may be distressing or dangerous to the individual experiencing them.
Drugs in this class have a phenylcyclohexylamine structure, and include abused substances such as phencyclidine and ketamine. These drugs produce a characteristic sense of detachment or dissociation from normal sensation and their surroundings.
They are capable of producing violent psychoses, particularly after heavy and repeated use. Like other hallucinogenics, acute psychosis associated with their use may be misdiagnosed as a first presentation of schizophrenia, particularly in younger users. There is a large degree of variation in the effect they produce for a given dose. They are relatively easy to synthesise and cheap, sometimes being passed off as more expensive LSD.
Ketamine was also originally developed as an anaesthetic agent, but unlike phencyclidine it is still used for this purpose today. Because of a high incidence of postoperative confusion and hallucinations, its routine use is not recommended. However, it is still regarded as a useful anaesthetic induction agent because of some very useful and almost unique properties. Unlike most other anaesthetic agents, it can be injected intramuscularly when intravenous access is problematic.
Ketamine is also used in some patients with chronic pain. Given as a ‘bolus’ intravenously over a period of a few days, it may enhance the effects of opioid drugs, particularly in patients with terminal illness; Correll et al  also looked at its use in Complex Regional Pain Syndrome. It is also occasionally used orally for patients with chronic non-malignant pain. However, its dissociative effects can cause distressing side effects.
When sold illicitly it is known by its street name of ‘K’ or ‘Special K’. It is typically injected, and produces vivid hallucinations. Hyperreflexia and increased muscle tone are often seen after use. Individuals may remain motionless for prolonged periods, again producing symptoms that are sometimes confused with schizophrenia.
Unlike most other abused drugs, the main motivation for self-administration of steroids is usually to attain an increase in muscular power and stamina . However, they also have mood-altering effects and addictive potential. Euphoria and elevation of mood may be observed , but rapid changes in mood and aggression are also common .
Street steroids are made available from a variety of sources, which include re-sold prescription drugs, illicit suppliers and agricultural and veterinary sources. Agricultural and veterinary drugs are often used to increase the sale weight of cattle; there is little published data on their effects in man.
Chronic use of anabolic steroids is associated with masculinising effects in women (deepened voice, clitoral enlargement, reduction in breast size)  and feminising effects in men (decreased size of testes, decreased sperm production and breast development) . There is an increase in aggression and combativeness , which is seen as an advantage in contact sports but a disadvantage in personal relationships and social interaction. There have been numerous reports of spontaneous acts of violence which have subsequently been blamed on the effects of these drugs. Chronic anabolic steroid use also produces other harmful effects on health.
There is a reported increased incidence of acute myocardial infarction, and an association with liver disease . There are other harmful changes such as osteoporosis, poor wound healing, weight gain and diabetes that have been extensively reported as side effects of chronic therapeutic use .
A substantial number of drugs are taken in combination to produce a variety of effects. Combinations such as ‘speedball’ (heroin and cocaine) are popular in the U.S. The combination produces profound euphoria, while the sedative effects of the heroin tend to reduce what many users regard as the unpleasant peripheral sympathetic side-effects of cocaine, such as restlessness and panic attacks.
Drug users often use different drugs at different times to counter the side effects or the withdrawal periods: ‘uppers’ may be interspersed with ‘downers’ for example.
Other combinations are taken to promote particular effects. MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD (known as ‘candy flipping’), ketamine (known as ‘kitty flipping’) or common drugs such as cannabis. Many users use mentholated products such as Vicks or lozenges while taking MDMA for a cooling sensation while experiencing the drug’s effects.
“Blue Velvet” is a combination of morphine, dihydrocodeine or codeine with an antihistamine (tripelennamine) usually injected but also may be swallowed or used as a retention enema.
Polydrug use is common amongst persistent misusers.
For more information on alcohol see www.rcpsych.ac.uk/PDF/pfacalc.pdf
For further information about prescription drug abuse including opioid and benzodiazepine abuse and misuse, consult Wilford et al , Isaacson , Longo & Johnson , Longo et al  Hser et al  and National Institute of Drug Abuse , , , .
See also Controlled Drugs in Primary Care http://www.controlleddrugs.org/usefulpublications.html
For briefer summaries see http://www.drugsline.org/outreach_effects.php
For a good review of the neurological complications of drug abuse, consult Neiman et al  and for information about ‘club drugs’ such as ‘ecstasy’, ketamine, GHB, etc consult Drug Enforcement Administration .
http://www.rcpsych.ac.uk/files/samplechapter/44_7.pdf is a Royal College of Psychiatry resource with information about the main drugs.
For further information about hallucinogenics consult National Institute on Drug Abuse .
For NICE Guidelines on opiate detoxification see http://guidance.nice.org.uk/CG52%20
- Klatsky, A.L., Friedman, G.D., Siegelaub, A.B., 1978. Alcohol and hypertension. Compr Ther, Compr Ther 4, 60-8.
Thomas, V.S., Rockwood, K.J., 2001. Alcohol abuse, cognitive impairment, and mortality among older people. J Am Geriatr Soc, J Am Geriatr Soc 49, 415-20.
- Hermann, D., Heinz, A., Mann, K., 2002. Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism. Addiction, Addiction 97, 1369-81.
Kannel, W.B., McGee, D., Gordon, T., 1976. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol, Am J Cardiol 38, 46-51.
- Gilson, A.M., Ryan, K.M., Joranson, D.E., Dahl, J.L., 2004. A reassessment of trends in the medical use and abuse of opioid analgesics and implications for diversion control: 1997-2002. J Pain Symptom Manage, J Pain Symptom Manage 28, 176-88.
- Manchikanti, L., Cash, K.A., Damron, K.S., Manchukonda, R., Pampati, V., McManus, C.D., 2006. Controlled substance abuse and illicit drug
- use in chronic pain patients: An evaluation of multiple variables. Pain Physician, Pain Physician 9, 215-25.
- Schifano, F., Zamparutti, G., Zambello, F., Oyefeso, A., Deluca, P., Balestrieri, M., Little, D., Ghodse, A.H., 2006. Review of deaths related to analgesic- and cough suppressant-opioids; England and Wales 1996-2002. Pharmacopsychiatry, Pharmacopsychiatry 39, 185-91.
- Sullivan, M.D., Edlund, M.J., Fan, M.Y., Devries, A., Braden, J.Brennan, Martin, B.C., 2008. Trends in use of opioids for non-cancer pain
- conditions 2000-2005 in commercial and Medicaid insurance plans: the TROUP study. Pain, Pain 138, 440-9.
- Edlund, M.J., Martin, B.C., Fan, M.Y., Devries, A., Braden, J.B., Sullivan, M.D., 2010. Risks for opioid abuse and dependence among recipients of chronic opioid therapy: Results from the TROUP Study. Drug Alcohol Depend, Drug Alcohol Depend. doi:10.1016/j.drugalcdep.2010.05.017
- Frei, M.Y., Nielsen, S., Dobbin, M.D., Tobin, C.L., 2010. Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen
- analgesics: a series of 27 cases. Med J Aust, Med J Aust 193, 294-6.
- Carson, H.J., Knight, L.D., Dudley, M.H., Garg, U., 2010. A fatality involving an unusual route of fentanyl delivery: Chewing and aspirating the
- transdermal patch. Leg Med (Tokyo), Leg Med (Tokyo) 12, 157-9. doi:10.1016/j.legalmed.2010.03.001
Koesters, S.C., Rogers, P.D., Rajasingham, C.R., 2002. MDMA (‘ecstasy’) and other ‘club drugs’. The new epidemic. Pediatr Clin North Am,
- Pediatr Clin North Am 49, 415-33.
- Bolla, K.I., McCann, U.D., Ricaurte, G.A., 1998. Memory impairment in abstinent MDMA (“Ecstasy”) users. Neurology, Neurology 51, 1532-7.
McCann, U.D., Mertl, M., Eligulashvili, V., Ricaurte, G.A., 1999. Cognitive performance in (+/-) 3,4-methylenedioxymethamphetamine (MDMA,
- “ecstasy”) users: a controlled study. Psychopharmacology (Berl), Psychopharmacology (Berl) 143, 417-25.
- Harries, D.P., De Silva, R., 1992. ‘Ecstasy’ and intracerebral haemorrhage. Scott Med J, Scott Med J 37, 150-2.
- Gledhill, J.A., Moore, D.F., Bell, D., Henry, J.A., 1993. Subarachnoid haemorrhage associated with MDMA abuse. J Neurol Neurosurg
- Psychiatry, J Neurol Neurosurg Psychiatry 56, 1036-7.
- Manchanda, S., Connolly, M.J., 1993. Cerebral infarction in association with Ecstasy abuse. Postgrad Med J, Postgrad Med J 69, 874-5.
- Hatzidimitriou, G., McCann, U.D., Ricaurte, G.A., 1999. Altered serotonin innervation patterns in the forebrain of monkeys treated with
- (+/-)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. J Neurosci, J Neurosci 19, 5096-107.
- Hopkins, P.M., Ellis, F.R., Halsall, P.J., 1991. Evidence for related myopathies in exertional heat stroke and malignant hyperthermia. Lancet, Lancet 338, 1491-2.
- O’Regan, M.C., Clow, A., 2004. Decreased pain tolerance and mood in recreational users of MDMA. Psychopharmacology (Berl),
- Psychopharmacology (Berl) 173, 446-51.
- Cowan, R.L., 2007. Neuroimaging research in human MDMA users: a review. Psychopharmacology (Berl), Psychopharmacology (Berl) 189,
- Thomasius, R., Zapletalova, P., Petersen, K., Buchert, R., Andresen, B., Wartberg, L., Nebeling, B., Schmoldt, A., 2006. Mood, cognition and
- serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective. J Psychopharmacol, J
- Psychopharmacol 20, 211-25.
Morgan, M.J., Impallomeni, L.C., Pirona, A., Rogers, R.D., 2006. Elevated impulsivity and impaired decision-making in abstinent Ecstasy
- (MDMA) users compared to polydrug and drug-naive controls. Neuropsychopharmacology, Neuropsychopharmacology 31, 1562-73.
- Pirona, A., Morgan, M.J., 2010. An investigation of the subacute effects of ecstasy on neuropsychological performance, sleep and mood in
- regular ecstasy users. J Psychopharmacol, J Psychopharmacol 24, 175-85.
- Blair, S.D., Holcombe, C., Coombes, E.N., O’Malley, M.K., 1991. Leg ischaemia secondary to non-medical injection of temazepam. Lancet,
- Lancet 338, 1393-4.
- Misuse, N.Treatment, 2007. Drug Misuse and dependence – UK guidelines on clinical management Department of Health.
- Green, B.E., Ritter, C., 2000. Marijuana use and depression. J Health Soc Behav, J Health Soc Behav 41, 40-9.
- Masters, A.B., Hoffer, A., Nair, N.P., Messer, C.J., Zarsadias, R., Moraes, C., 1971. Care of chronic psychotics. Br Med J, Br Med J 4, 489.
Kast, E., 1967. Attenuation of anticipation: a therapeutic use of lysergic acid diethylamide. Psychiatr Q, Psychiatr Q 41, 646-57.
- Sewell, R.A., Halpern, J.H., Pope, Jr., H.G., 2006. Response of cluster headache to psilocybin and LSD. Neurology, Neurology 66, 1920-2.
Correll, G.E., Maleki, J., Gracely, E.J., Muir, J.J., Harbut, R.E., 2004. Subanesthetic ketamine infusion therap
- y: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med, Pain Med 5, 263-75.
- Blue, J.G., Lombardo, J.A., 1999. Steroids and steroid-like compounds. Clin Sports Med, Clin Sports Med 18, 667-89, ix.
- Pope, Jr., H.G., Kouri, E.M., Hudson, J.I., 2000. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a
- randomized controlled trial. Arch Gen Psychiatry, Arch Gen Psychiatry 57, 133-40; discussion 155-6.
- Bahrke, M.S., ,, Wright, J.E., 1996. Psychological and behavioural effects of endogenous testosterone and anabolic-androgenic steroids. An update. Sports Med, Sports Med 22, 367-90.
- Gruber, A.J., Pope, Jr., H.G., 2000. Psychiatric and medical effects of anabolic-androgenic steroid use in women. Psychother Psychosom,
- Psychother Psychosom 69, 19-26.
- Sullivan, M.L., Martinez, C.M., Gennis, P., Gallagher, E.J., 1998. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis, Prog Cardiovasc Dis 41, 1-15.
- Abuse, N.Institute, 2000. Anabolic steriod abuse.
- Wilford, B.B., Finch, J., Czechowicz, D.J., Warren, D., 1994. An overview of prescription drug misuse and abuse: defining the problem and
- seeking solutions. J Law Med Ethics, J Law Med Ethics 22, 197-203.
Isaacson, J.H., 2000. Preventing prescription drug abuse. Cleve Clin J Med, Cleve Clin J Med 67, 473-5.
- Longo, L.P., Johnson, B., 2000. Addiction: Part I. Benzodiazepines–side effects, abuse risk and alternatives. Am Fam Physician, Am Fam
- Physician 61, 2121-8.
- Longo, L.P., Parran, Jr., T., Johnson, B., Kinsey, W., 2000. Addiction: part II. Identification and management of the drug-seeking patient. Am
- Fam Physician, Am Fam Physician 61, 2401-8.
- Hser, Y.I., Hoffman, V., Grella, C.E., Anglin, M.D., 2001. A 33-year follow-up of narcotics addicts. Arch Gen Psychiatry, Arch Gen Psychiatry 58,
- Abuse, N.Institute, 1999. Cocaine abuse and addiction.
Abuse, N.Institute, 2001. Hallucinogens and dissociative drugs.
- Abuse, N.Institute, 2001. Prescription drug abuse and addiction.
- Neiman, J., Haapaniemi, H.M., Hillbom, M., 2000. Neurological complications of drug abuse: pathophysiological mechanisms. Eur J Neurol,
- Eur J Neurol 7, 595-606.
- Administration, D.Enforcemen, 2000. Drug Intelligence Brief.