Amphetamine treatment for obesity refers to the historical use of central nervous system stimulants to suppress appetite and promote weight loss. Whilst these medications were once prescribed for weight management, they are no longer recommended or licensed for obesity treatment in the UK due to significant safety concerns, including cardiovascular risks, psychiatric effects, and high potential for dependence. Current NHS and NICE guidelines do not support amphetamine use for weight loss, instead recommending evidence-based alternatives such as lifestyle modification, orlistat, GLP-1 receptor agonists like semaglutide, and bariatric surgery for eligible patients. Understanding why amphetamines are unsuitable for obesity management helps patients and healthcare professionals make informed decisions about safe, effective weight loss strategies.

What Are Amphetamines and How Do They Work for Weight Loss?

Amphetamines are a class of central nervous system stimulants that have historically been used in the treatment of obesity, though their use for this indication has become increasingly restricted in the UK and internationally. These medications work primarily by affecting neurotransmitter systems in the brain, particularly dopamine and noradrenaline pathways, which influence appetite regulation and energy expenditure.

The mechanism of action for weight loss involves several physiological processes. Amphetamines suppress appetite by stimulating the release of noradrenaline in the hypothalamus, the brain region responsible for hunger and satiety signals. This leads to reduced food intake and decreased caloric consumption. Additionally, these medications may modestly increase metabolic rate through sympathetic nervous system activation. The stimulant properties may also reduce fatigue, which could indirectly influence activity levels, though these effects vary considerably between individuals.

In the UK, amphetamine-based medications are not licensed for obesity and are rarely prescribed due to significant safety concerns and the availability of safer alternatives. Historically, drugs such as dexamfetamine and amphetamine mixtures were used for short-term weight management, but their potential for dependence, cardiovascular risks, and adverse psychiatric effects have led to their withdrawal from routine obesity treatment. Amphetamines are Schedule 2 controlled drugs under the Misuse of Drugs Regulations 2001, and prescribing must comply with controlled drug requirements. These medications are now reserved for specific licensed indications such as attention deficit hyperactivity disorder (ADHD) and narcolepsy, rather than weight management.

It is important to understand that whilst amphetamines can produce rapid weight loss, this effect is typically temporary and accompanied by substantial health risks that generally outweigh the benefits for obesity treatment.

NHS Guidelines on Amphetamine-Based Obesity Treatments

The NHS does not currently recommend amphetamines as a treatment option for obesity management. National Institute for Health and Care Excellence (NICE) guidelines on obesity (CG189: Obesity: identification, assessment and management) do not include amphetamine-based medications in their recommended pharmacological interventions for weight management. This position reflects the consensus amongst UK healthcare authorities that the risks associated with amphetamine use significantly outweigh any potential benefits for obesity treatment.

NICE guidelines instead recommend a structured approach to obesity management that prioritises lifestyle interventions, including dietary modification, increased physical activity, and behavioural support. When pharmacological treatment is considered appropriate, NICE recommends specific anti-obesity medications such as orlistat (a lipase inhibitor) as a first-line option for adults with a body mass index (BMI) of 30 kg/m² or above, or 28 kg/m² or above with associated risk factors. Treatment with orlistat should be continued beyond 3 months only if the person has lost at least 5% of their initial body weight since starting drug treatment (unless there are adequate improvements in glycaemic control in people with type 2 diabetes). More recently, glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide 2.4 mg (Wegovy) have been recommended by NICE (TA875) for weight management in specialist weight management services for adults with at least one weight-related comorbidity and a BMI of at least 35 kg/m² (or 32.5 kg/m² for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds), typically for up to 2 years.

The British National Formulary (BNF) classifies amphetamines as Schedule 2 controlled drugs under the Misuse of Drugs Regulations 2001, reflecting their high potential for abuse and dependence. Prescribing of amphetamines for any indication requires careful justification and adherence to controlled drug regulations. For obesity specifically, amphetamines are not licensed for use in the UK, and prescribing these medications off-label for weight loss is not recommended, is outside licensed indications and UK guidance, and carries significant safety and medico-legal concerns.

Patients seeking weight management support through the NHS should expect a comprehensive assessment that considers underlying causes of obesity, comorbidities, and individualised treatment plans that align with current evidence-based guidelines. Healthcare professionals are advised to discuss realistic weight loss goals and the importance of sustainable lifestyle changes rather than pharmacological shortcuts that carry significant health risks.

Effectiveness and Clinical Evidence for Weight Management

Whilst amphetamines can produce measurable weight loss in the short term, the clinical evidence supporting their use for obesity treatment is limited and largely historical. Early studies from the mid-20th century demonstrated that amphetamine-based medications could produce modest weight reductions over periods of several weeks to months. However, these studies were often methodologically limited, with small sample sizes, short follow-up periods, and inadequate assessment of long-term outcomes or safety profiles.

A critical limitation of amphetamine treatment for obesity is the development of tolerance. Most patients experience diminishing appetite suppression effects within weeks to months of continuous use, as the body adapts to the medication's pharmacological effects. This tolerance necessitates dose escalation to maintain weight loss, which increases the risk of adverse effects and dependence. Furthermore, weight regain is common upon discontinuation of amphetamine treatment, as the underlying behavioural and metabolic factors contributing to obesity remain unaddressed.

Contemporary systematic reviews have not established amphetamines as an effective long-term solution for obesity management. The evidence base is insufficient to support their use when compared to modern anti-obesity medications that have undergone rigorous clinical trials demonstrating sustained weight loss, improved metabolic parameters, and acceptable safety profiles. Studies of newer agents such as GLP-1 receptor agonists have shown superior outcomes, with weight reductions of approximately 15% of body weight at 68 weeks maintained over extended periods in clinical trials, alongside improvements in cardiovascular risk factors.

It is important to note that there is no official recommendation from UK regulatory bodies or clinical guidelines supporting amphetamine use for obesity. The lack of robust, long-term efficacy data, combined with well-documented safety concerns, has led to the consensus that amphetamines should not be considered a viable treatment option for weight management in modern clinical practice. Patients and healthcare professionals should focus on evidence-based interventions that offer sustainable results without the significant risks associated with amphetamine therapy.

Side Effects and Safety Considerations

Amphetamines carry a substantial burden of adverse effects that make them unsuitable for obesity treatment. The cardiovascular risks are particularly concerning and include elevated blood pressure, tachycardia (rapid heart rate), palpitations, and increased risk of arrhythmias. These effects result from the sympathomimetic action of amphetamines, which stimulate the cardiovascular system through increased noradrenaline release. Patients with pre-existing cardiovascular disease, hypertension, or structural heart abnormalities face significantly elevated risks of serious cardiac events, including myocardial infarction and sudden cardiac death. Baseline cardiovascular assessment, including blood pressure and heart rate measurement, is essential before initiating treatment, with regular monitoring thereafter. An ECG may be indicated in certain patients as per product information.

Psychiatric and neurological adverse effects are equally problematic. Common side effects include:

• Insomnia and sleep disturbances

• Anxiety, restlessness, and agitation

• Mood changes, including irritability and depression

• Tremor and motor tics

• Headaches and dizziness

More serious psychiatric complications can include psychosis, paranoia, and hallucinations, particularly at higher doses or with prolonged use. These effects may persist even after discontinuation and can be particularly severe in individuals with underlying mental health conditions.

The potential for dependence and addiction represents one of the most significant safety concerns with amphetamine use. These medications have high abuse liability, and regular use can lead to psychological and physical dependence. Withdrawal symptoms upon discontinuation may include severe fatigue, depression, increased appetite, and sleep disturbances, which can persist for weeks or months.

Other important adverse effects include:

• Gastrointestinal disturbances (dry mouth, nausea, constipation)

• Sexual dysfunction

• Growth suppression in children and adolescents (requiring regular height and weight monitoring)

• Hyperthermia (particularly associated with high doses, overdose, or misuse)

• Seizures in susceptible individuals

Patients should be aware that amphetamines are contraindicated in numerous conditions, including cardiovascular disease, hyperthyroidism, glaucoma, and history of substance abuse. Drug interactions are common and potentially dangerous, particularly with monoamine oxidase inhibitors (MAOIs), other stimulants, medications affecting blood pressure, and serotonergic medicines (such as SSRIs, SNRIs, triptans, and tramadol), which may increase the risk of serotonin syndrome. Anyone considering or currently using amphetamines should seek immediate medical attention if they experience chest pain, severe headache, shortness of breath, or psychiatric symptoms.

Patients and healthcare professionals are encouraged to report suspected adverse reactions via the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

Alternatives to Amphetamine Treatment for Obesity

Modern obesity management offers numerous evidence-based alternatives that are safer and more effective than amphetamines. The foundation of treatment remains lifestyle modification, which NICE guidelines recommend as the first-line approach for all patients with obesity. This includes structured dietary interventions targeting a caloric deficit of 600 kcal per day, increased physical activity in line with UK Chief Medical Officers' guidance (at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity activity per week, plus muscle-strengthening activities on at least 2 days per week), and behavioural therapy to address eating patterns and psychological factors contributing to weight gain.

When pharmacological intervention is appropriate, several licensed medications are available in the UK:

Orlistat is a lipase inhibitor that reduces dietary fat absorption by approximately 30%. It is available both on prescription (for adults with BMI ≥30 kg/m² or ≥28 kg/m² with risk factors) and over-the-counter (for adults aged 18 years and over with BMI ≥28 kg/m²). Whilst weight loss is modest (typically 2–3 kg additional loss compared to lifestyle intervention alone), orlistat has a well-established safety profile with primarily gastrointestinal side effects. Treatment should be continued beyond 3 months only if at least 5% of initial body weight has been lost (unless there are adequate improvements in glycaemic control in people with type 2 diabetes).

GLP-1 receptor agonists, particularly semaglutide 2.4 mg (Wegovy), represent a significant advancement in obesity pharmacotherapy. These medications work by mimicking natural gut hormones that regulate appetite and glucose metabolism. Clinical trials have demonstrated weight reductions of approximately 15% of body weight at 68 weeks, with improvements in cardiovascular risk factors. Semaglutide 2.4 mg is administered as a weekly subcutaneous injection and is recommended by NICE (TA875) for adults with at least one weight-related comorbidity and a BMI of at least 35 kg/m² (or 32.5 kg/m² for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds), within specialist weight management services (Tier 3), typically for up to 2 years. Liraglutide 3 mg is also available under more restricted criteria (NICE TA664) for a narrower patient group.

Bariatric surgery remains the most effective intervention for severe obesity (BMI ≥40 kg/m² or ≥35 kg/m² with comorbidities that could be improved with weight loss; lower thresholds apply for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds). Procedures such as gastric bypass and sleeve gastrectomy can produce sustained weight loss of 25–30% of body weight and significant improvements in obesity-related conditions including type 2 diabetes, hypertension, and sleep apnoea. Referral to specialist weight management services (Tier 3) is recommended for assessment and preparation, with progression to bariatric surgery services (Tier 4) for eligible patients.

Additional support options include:

• NHS-funded weight management programmes (Tier 2) offering structured group support

• Psychological interventions such as cognitive behavioural therapy (CBT) for binge eating disorder

• Dietitian-led nutritional counselling

• Commercial weight management programmes (some available on NHS referral)

Patients should consult their GP for a comprehensive obesity assessment and discussion of appropriate treatment options tailored to their individual circumstances, medical history, and weight loss goals. Sustainable weight management requires a long-term commitment to lifestyle changes, and healthcare professionals can provide ongoing support and monitoring to optimise outcomes whilst minimising health risks.

Frequently Asked Questions