31st January 2024

Substance misuse

Substance Misuse

NICE guidance defines substance misuse as frequent and excessive consumption of psychoactive substances, as well as intoxication by and dependence on these substances (NICE, 2022), which can result in psychosocial and physical health complications. Substance misuse patterns vary across the UK; cannabis, cocaine, and ecstasy are currently the most misused substances; however, opioids present the most harmful health profile. The UK also has higher rates of heroin misuse compared to other Western countries, as well as higher rates of overdose-related death.

Alongside alcohol use, substance misuse is also more prevalent in lower socioeconomic areas and associated with worse physical health outcomes, e.g., blood-borne infections secondary to injecting heroin. Therefore, it is important that any intervention and management plans focus on improving quality of life, supporting recovery, reducing risk and preventing premature death. Groups that may require more comprehensive assessment include prison occupants and the homeless, particularly when considering issues such as injecting practice, as these groups are more vulnerable to complications that can arise, e.g., infection risks from sharing needles. NICE have identified several quality statements in relation to substance misuse and dependence, which are designed to improve the safety and care of those affected. These statements include:

Source: Adapted from Drug use disorders in adults [Internet]. NICE. 2012 [cited 2022Dec3]. Available from: https://www.nice.org.uk/Guidance/QS23

Risk assessment is a key part of substance misuse management. This should include:

1. Consideration of overdose risk.
2. Assessing for polydrug use and coinciding alcohol misuse.
3. Screening for common coexisting mental health conditions.
4. Assessing for unsafe injecting practices.
5. Considering safeguarding issues, e.g., any dependents.

Treatment for drug misuse should take a holistic approach and always include a psychosocial component. Some current evidence-based interventions include contingency management (CM) and behavioural couples therapy (BCT).

References

• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Drug use disorders in adults [Internet]. NICE. 2012 [cited 2022Dec3]. Available from: https://www.nice.org.uk/Guidance/QS23

Cannabis 

Background

Cannabis is one of the most ingested illicit substances worldwide, and dependence is relatively common. This section will not cover any of the medicinal uses of cannabis.

Tetrahydrocannabinol (THC) is a cannabinoid compound within cannabis that binds to cannabinoid receptors, modulating inhibition of various neurotransmitters, which in turn influences mood, appetite, etc. It is normally released when cannabis is smoked and distributed throughout the body via perfusion with rapid effect on the neural transmitters described above. When ingested orally, distribution is slower, and peak concentrations are reached later. It is a lipophilic compound and, therefore, can accumulate in the body for a long period of time.

Presentation 

Features of acute intoxication include anxiety, increased appetite/cravings, dry mouth and impaired cognitive and psychomotor functioning. Some may also experience rarer effects, such as hallucinations, delusional thoughts and acute psychosis. Withdrawal and/or chronic use can result in lethargy, low mood, agitation, loss of interest and motivation and poor concentration/memory. These symptoms can profoundly impact the life of the person affected, making it difficult to maintain relationships, keep employment and engage in formal education. It is important to remember that independent mood disorders can exist alongside cannabis misuse, and symptoms must be carefully evaluated before any diagnosis is made.

Diagnosis

A careful history will need to be taken, identifying if any cannabis-containing products were ingested, if a similar presentation has been noted before and if any other substances have also been taken. As with many other substance misuse presentations, diagnosis is largely clinical but also relies on collateral information and history gained from the patient if possible. Cannabis can also be tested for in urine – occasional use can be detected for 1-3 weeks, but chronic use can be detected for up to 12 weeks.

Differential diagnosis

Psychosis that can occur with heavy cannabis use could mimic some of the signs and symptoms of schizophrenia,  but the apathy and lethargy that can follow prolonged use could also present similarly to depression.

Management 

Treatment options are largely supportive in nature, with the aim of improving function and mood. If able, sobriety will be encouraged, although a gradual tapering of cannabis use may be favoured to try and avoid withdrawal symptoms. In acute intoxication, symptomatic treatment can be offered as needed, e.g., ensuring a quiet, calm space is available; however, the intoxication usually resolves without any formal intervention.

Psychological therapies can be offered both to support recovery and rehabilitation and, if needed, address any co-occurring/underlying mental health conditions, such as depression, which can become more apparent with abstinence.

References 

• Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020.
• Patel, J. and Marwaha, R. (2022) Cannabis use disorder, National Center for Biotechnology Information. U.S. National Library of Medicine. Available at: https://pubmed.ncbi.nlm.nih.gov/30844158/ (Accessed: December 27, 2022).
• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.

Stimulants

Background

Stimulants are another substance classification commonly used recreationally. They include ecstasy (MDMA), amphetamines and cocaine. Some amphetamines, such as dexamphetamine, have been prescribed for Attention Deficit Hyperactivity Disorder (ADHD). They enhance the release of serotonin, dopamine and norepinephrine  (monoamine) neurotransmitters by blocking reuptake, resulting in increased levels within neural synapses. The excess release of these neurotransmitters causes the euphoria commonly experienced when they are ingested, increasing the risk of dependence. However, after prolonged use, levels of these neurotransmitters become depleted, causing long-term effects on cognition and mood.

MDMA reaches peak concentration in the blood approximately 2 hours post-ingestion and undergoes hepatic metabolism; however, it has an extensive half-life, which may account for the longevity of symptoms.

Amphetamines were first marketed as a treatment for nasal congestion; however, due to their high abuse potential, very few today remain medically licensed, e.g., for the treatment of narcolepsy or Parkinson’s disease. They can be injected, smoked or taken orally.

Cocaine is sourced from the coca plant and can be ingested orally, nasally or injected. The effects last up to one hour after consumption, and it has a short half-life. Topically, cocaine can have an anaesthetic effect as well as cause vasoconstriction, but if enough is absorbed systemically, alpha and beta adrenoreceptors may be stimulated, which causes tachycardia.

Presentation

Intoxication can cause insomnia, euphoria, agitation, headache, poor appetite, and mydriasis. Toxicity can result in seizures, psychosis, chest pain and strokes. Withdrawal can cause a ‘crash,’ lethargy and low mood.

Co-administration of amphetamines with other serotonergic drugs can cause serotonin syndrome and, if taken within 2 weeks of a MAOI, can cause a hypertensive crisis.

Diagnosis

Urine testing can detect traces of most stimulants for 2-3 days. Patients presenting with tachycardia will require an ECG to explore this, and any seizures or reduced consciousness will need to be managed and investigated, e.g., via CT head.

Differential diagnosis

The effects of stimulant use can mimic independent psychiatric disorders, such as anxiety, panic disorder, and the mania phase of bipolar disorder. Drug-induced psychosis can also occur.

Management 

Aside from the acute management required if a person presents severely unwell after stimulant use/withdrawal, psychosocial intervention and harm reduction are the key components of management for stimulant misuse. Any side effects from stimulant misuse and/or withdrawal, including acute co-presenting or coexisting psychiatric disorders, should be managed symptomatically as indicated, with reassurance and support offered. Specific targeted pharmacological therapies have been explored in relation to management of stimulant misuse; however, to date, there is little evidence that these have been effective in supporting and maintaining sobriety, hence the current recommendation for psychosocial interventions to remain the mainstay of treatment. Safety advice should also be given, e.g., in relation to injection safety if the substances are being taken intravenously.

References

• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Vasan S, Olango GJ. Amphetamine Toxicity. StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470276/
• NIDA. “What are MDMA’s effects on the brain?.” National Institute on Drug Abuse, 13 Apr. 2021, https://nida.nih.gov/publications/research-reports/mdma-ecstasy-abuse/what-are-mdmas-effects-on-brain Accessed 3 Dec. 2022.
• CAMH. Amphetamines [Internet]. Centre for Addiction and Mental Health. 2012 [cited 2022Dec3]. Available from: https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/amphetamines
• Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. CMAJ. 2001;165(7):917-928.
• Martin D, Le JK. Amphetamine.StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556103/
• Richards JR, Laurin EG. Cocaine. StatPearls. 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430769/

Sedatives

Background

This class of substances includes benzodiazepines and other substances such as Z-hypnotics and barbiturates. They are typically prescribed for short-term treatment of anxiety or insomnia and can also be used as a form of sedation for medical procedures. However, the feelings of elation they induce make them a commonly abused class of medications., and many people can remain on them for several years. It is recognised that they have a harmful side effect profile, and where able, efforts should be made to encourage cessation. They act on GABA receptors, increasing the effect of this inhibitory neurotransmitter.

Presentation 

Sedative use can cause sedation, speech impairment, inattention, reduced anxiety, euphoria, ataxic gait, mydriasis, respiratory depression and coma (in overdose). Withdrawal can cause seizures, tremor and hallucinations.

Diagnosis

As previously discussed, a careful history and examination will be required if a person presents with signs and/or symptoms of sedative overdose or withdrawal. Where required, a neurological examination and delirium screen may be needed, depending on presentation, as well as a workup for any other suspected cause of symptoms. Short-acting benzodiazepines can be detected in urine for 1-3 days, whereas long-acting benzodiazepines can be detected for up to 6 weeks post-ingestion.

Differential diagnosis

The gait imbalance and hyporeflexia that can occur could mimic a stroke event, and seizures or hallucinations could also have an organic component that would need to be ruled out via appropriate investigation, such as CT head. Withdrawal could also mimic alcohol withdrawal, especially if seizures occur.

Management

The dependence-inducing properties are related to the dose and duration of sedative use, and long-term prescribing of these drugs is not considered to be beneficial. To prevent withdrawal, clinicians should continue a current prescription but gradually taper the dose down, until the medication has been stopped. Benzodiazepines specifically can be tapered down by ⅛ of the daily dose every 2 weeks; however, this should be guided by the patient’s symptoms and may take several months to achieve.

Benzodiazepine overdose specifically can be treated with flumazenil, which acts as a benzodiazepine antagonist; however, it can provoke seizures and is quite short-acting. Withdrawal can produce sudden and severe symptoms, hence the need for gradual tapering and cessation. In emergency presentations, such as where an airway is compromised, an A to E approach should be followed in the first instance, and senior help sought.

If methadone is being taken concurrently with sedatives, this dose should be kept stable whilst sedative dosing is altered, if needed, to avoid dual detoxification. Physical and mental health issues that may have prompted sedative use initially should also be addressed as part of wider management and to support abstinence, e.g., psychosocial therapies, counselling and support groups.

References

• Weaver MF. Prescription Sedative Misuse and Abuse. Yale J Biol Med. 2015;88(3):247-256.
• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020.

Hallucinogens

Background

Several thousand compounds have hallucinogenic properties; these substances can also be referred to as ‘psychedelics.’ Some naturally occur in plants and fungi (such as psilocybin), and others are synthetic in nature (such as LSD, PCP and ketamine).

Hallucinogens can act on both dopamine and serotonin receptors, by increasing the concentration of the neurotransmitters available. Some studies have found that these compounds are ‘psychotomimetic,’ meaning that acute intoxication can cause a temporary psychotic presentation, but potentially also predispose to a syndrome in keeping with a true psychotic disorder. It is proposed that hallucinogen-induced psychosis is associated with higher levels of dopamine.

Presentation

The effects of each hallucinogen will depend on the substance itself and quantity ingested. Common side effects of hallucinogens are visual, auditory and tactile sensory disturbances, altered experience of time and altered perception of objects. For some individuals, mood changes can occur, as well as temporary cognitive impairment.

Dependence is rare, and withdrawal has not been described; most morbidity is due to intoxication. The most common mental disorder related to hallucinogen use is hallucinogen-induced psychotic disorder.

Acute intoxication with hallucinogens is primarily a clinical diagnosis.

Differential diagnosis 

The potential visual and/or auditory sensory disturbances that can be caused by hallucinogen use could mimic an independent psychiatric disorder, such as a form of psychosis. Other substances, such as cannabis, could also cause a similar symptom profile, and concurrent use should be explored as part of management.

Management

At present, as for cannabis and stimulant misuse, psychosocial therapy is the mainstay of treatment for the misuse of hallucinogens, as well as supportive care for any distressing symptoms.

References

• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Fiorentini A, Cantù F, Crisanti C, Cereda G, Oldani L, Brambilla P. Substance-induced psychoses: An updated literature review. Frontiers in Psychiatry. 2021;12.
• Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020.

Opiates

Background

Opioids are classed as substances derived from the opium poppy and a range of synthetic and semi-synthetic compounds that primarily act on the μ opioid receptor. Examples include heroin, morphine and codeine. They all have analgesic effects and suppress respiration, which in some cases can be beneficial, e.g., use of Oramorph to treat shortness of breath as part of palliative symptom management. However, they are one of the most widely abused substances worldwide and have a dangerous side effect profile. Management of overdose, intoxication and withdrawal can be challenging and requires an MDT approach.

Presentation

Acute intoxication with opioids causes euphoria and sedative effects. Nausea, vomiting, dizziness, bradycardia, miosis and respiratory depression can also occur, especially if an IV preparation of opioid is used.

Opiate withdrawal can cause fatigue, coryzal symptoms, restlessness and irritability. Tremor, hypertension, tachycardia, nausea and mydriasis may also be seen. Withdrawal from IV heroin typically starts around six hours after injection and peaks at 36 to 48 hours. Scales available to rate opioid withdrawal severity include the Clinical Opiate Withdrawal Scale (COWS) and the Short Opiate Withdrawal Scale (SOWS)

Opioid dependence can be defined by the following ICD-10 criteria:

• Feeling the need/desire to take opioids (prescribed or otherwise)
• An inability to control the level or cessation of opioids
• Withdrawal symptoms  if opioids are not used for a period
• Opioid tolerance development
• Social withdrawal due to opioid use and needing to spend time both recovering from the side effect profile and obtaining more opioids
• Continuing to use opioids despite evidence of their negative effect, e.g., low mood

Diagnosis 

Diagnosis of acute opioid intoxication or withdrawal is largely clinical; however, urine sample testing can be used. Buprenorphine can be detected for 1-2 weeks post ingestion, methadone for 3-4 days, opiates like morphine for 2-3 days, and oxycodone for 1-2 days. Opioid dependence can be identified by considering the above ICD-10 criteria described.

Differential diagnosis

The physical symptoms of intoxication, such as nausea and vomiting, could mimic cerebellar syndromes, and the depressive effects can also mimic the action of benzodiazepines. Withdrawal symptoms such as tachycardia could present similarly to an arrhythmia, and should be explored via appropriate investigation, e.g., ECG.

Management

Opioid overdose

Overdose can be managed with naloxone if needed, for example, for patients presenting with reduced GCS at risk of airway compromise. This should be given in a stepwise approach to avoid precipitating withdrawal, due to the risk of recurrence of dangerous levels of sedation when the naloxone effect subsides (about 30-60 mins). Individuals with heroin dependence should be given overdose awareness training and take-home naloxone alongside opioid substitution therapy to increase safety practices.

Opioid withdrawal

Lofexidine is a non-opioid alpha-adrenergic agonist that can be used to manage symptoms of opioid withdrawal. NICE recommends its use for patients who have declined opioid substitution, wish to detoxify quickly or have only mild or uncertain dependence. Side effects include dry mouth and drowsiness, hypotension and bradycardia.

Opioid substitution

Opioid substitution (via a service referral) should be considered if the following criteria are met:

1. Regular opiate use (often daily).
2. Convincing evidence of current dependence.
3. Ability to comply with the substitution regimen.
4. Not receiving opioid substitution from an alternative source/clinician.

Methadone or buprenorphine can be used as opioid substitution treatment for opioid dependence. Initiation of treatment should be titrated to achieve a dose that avoids intoxication, withdrawal and leads to complete cessation of illicit opioid use. For methadone, this typically takes two to four weeks, but titration of buprenorphine is usually faster. In general, a typical starting dose of methadone would be 10-30mg, and a typical starting dose of buprenorphine would be 4-8 mg. An average maintenance dose of methadone would be between 60 and 120 mg daily, and an average maintenance dose of buprenorphine would be between 12 and 16 mg daily.

Methadone has full agonist properties and is a liquid preparation. Tablet form is available for special circumstances, e.g., to reduce nausea and vomiting. Ultra-long-acting forms like depot aren’t approved for UK use yet. It has a half-life of 13-50 hours, so delayed toxicity can occur; therefore, careful monitoring and dose adjustment are needed during initiation. Buprenorphine is a sublingual tablet with partial agonist and antagonist properties. There is a risk of precipitated withdrawal if the first dose is given when circulating opioids are still present due to the antagonist properties; therefore, the first dose should be given when withdrawal begins (6-12 hours after last opioid use). Both are metabolised by P450 enzymes so prone to drug interactions.

NICE recommends both methadone and buprenorphine. Evidence suggests buprenorphine is associated with lower incidence of fatal overdose during the start of treatment initiation but that more patients remain engaged with treatment when methadone is used. Other factors to consider when choosing which to initiate would include patient preference, any previous treatment failure and existing medication/alcohol interactions. Once established on maintenance treatment, the risk of death by overdose is considerably lower than prior to treatment.

When patients on community opioid substitution are admitted to hospital it is important to independently clarify the patient’s dose and when their last dose was supervised to have been taken (with their key worker and pharmacy). Once this has been confirmed if they have been regularly taking the prescribed medication the same dose can be continued. They should also be given information about drug treatment services, blood-borne virus infections and how to prevent drug overdose. This is termed harm reduction and is an important part of opioid management to consider.

References

• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020.
• Opioid dependence [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://cks.nice.org.uk/topics/opioid-dependence/ 
• The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines [Internet]. World Health Organization. World Health Organization; 1992 [cited 2022Dec3]. Available from: https://apps.who.int/iris/handle/10665/37958 

Summary table

Source: Adapted from: Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020, Opioid dependence [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://cks.nice.org.uk/topics/opioid-dependence/, Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017, Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. CMAJ. 2001;165(7):917-928 and Patel, J. and Marwaha, R. (2022) Cannabis use disorder, National Center for Biotechnology Information. U.S. National Library of Medicine. Available at: https://pubmed.ncbi.nlm.nih.gov/30844158/ (Accessed: December 27, 2022).