The clinical presentation can somewhat vary depending on the drug used, but the persistent need for drug use despite potentially harmful consequences, inability to regulate the frequency of its consumption and prioritizing its consumption over all other activities are hallmarks of drug dependence [1]. Two main types of dependence are recognized [2] [3]:

• Physical - Avoidance of undesired physical effects that occur due to the cessation of drug use, or withdrawal, are the primary reason for continuing drug use and development of dependence. Central nervous system hyperactivity, mydriasis, tremors, gastrointestinal irritation, and diarrhea are typical for opioid withdrawal, including heroin, while tachycardia, hyperreflexia, confusion, and seizures are reported after cessation of benzodiazepine use. Physical dependence is typical for cocaine, (presenting as a serious depressive reaction and intense fatigue accompanied by sleepiness) and alcohol, which usually manifests with CNS hyperactivity and constitutional symptoms, although more severe signs (hallucinations, delirium tremens) may be seen in severely dependent individuals.
• Psychological dependence - Euphoria, alleviation of anxiety, alterations in behavior, perception, and mental state, are the main features of dependence on hallucinogenic substances (lysergic acid, mescaline, psilocybin), marijuana, amphetamines and 3,4 -methylenedioxymethamphetamine (MDMA).

It is important to note that both physical and psychological dependence may be encountered in patients, making additional criteria highly useful in defining the diagnosis. Symptoms such as craving, tolerance (necessity to use larger amounts over time), repeated attempts to quit or control drug use, as well as giving up daily life activities due to dependence can be reported. When three or more symptoms are reported within a 12-month period, the diagnosis can be confirmed based on clinical criteria [2] [4].

• Weight Loss

  Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). [ncbi.nlm.nih.gov]

  Physical Loss or increase in appetite, change in eating habits, unexplained weight loss or gain Slowed or staggered walking, bumping into things Smell of alcohol on breath Slow or slurred speech Irregular sleep patterns, having difficulty sleeping, awake [sfad.org.uk]

  These problems can lead to difficulties in feeding, which can mean weight loss or failure to thrive. Difficulties with state regulation. [sheknows.com]

  Weight loss won’t eliminate your risk of a hernia, but it will ease the strain on your abdominal muscles. [healthline.com]

• Weight Gain

  It is due to weakened abdominal muscles, straining, and weight gain. This can occur in women, but men are eight to ten times more likely to be affected by an inguinal hernia than women. [study.com]

  Princeton University Press, Princeton Google Scholar Elliott SS, Keim NL, Stern JS et al (2002) Fructose, weight gain, and the insulin resistance syndrome. [doi.org]

  Acquired hernias are caused by the wear and tear of living, such as childbirth, weight gain, and other muscle strain. Congenital hernias are present from birth and happen at points of weakness in the abdominal wall. [herniaclinic.co.nz]

  Others are caused by excessive strain on the abdominal wall from heavy lifting, weight gain, coughing, or difficulty with bowel movements and urination. [generalsurgery.ucsf.edu]

• Cushingoid

  Both patients exhibited tolerance and withdrawal symptoms, and both developed serious systemic effects from the corticosteroids, including cataracts, diabetes mellitus, and cushingoid signs. [ncbi.nlm.nih.gov]

• Constitutional Symptom

  Physical dependence is typical for cocaine, (presenting as a serious depressive reaction and intense fatigue accompanied by sleepiness) and alcohol, which usually manifests with CNS hyperactivity and constitutional symptoms, although more severe signs [symptoma.com]

• Pseudotumor

  Two cases of prednisone dependence are reviewed; the first involving a patient with inflammatory orbital pseudotumor who developed a dependent pattern of prednisone use that persisted years after the resolution of the acute episode. [ncbi.nlm.nih.gov]

• Yawning

  Yawning. Being off food. Stomach cramps. Feeling sick (nausea) or being sick (vomiting). Diarrhoea. Tremor. Poor sleep. Restlessness. General aches and pains. Just feeling awful. Tolerance is usually a part of dependence. [patient.info]

  In addition, the March of Dimes also lists the symptoms: Fussiness, excessive crying or having a high-pitched cry Fever, sweating or blotchy skin Trouble sleeping and lots of yawning Stuffy nose or sneezing Treatment for babies Babies with NAS can be [sheknows.com]

  Opioid withdrawal Opioid withdrawal symptoms are caused by sympathetic overactivity and include tachycardia, anxiety, restlessness, insomnia, sweating, diarrhea, rhinorrhea, muscle aches, yawning, and “gooseflesh.” [journals.lww.com]

• Nausea

  As alcohol also irritates the stomach, heavy drinking can cause sickness and nausea, and sometimes diarrhoea. Alcohol also has a dehydrating effect, which is the main reason why excessive drinking can lead to a hangover. [ufs.ac.za]

  These symptoms include: anxiety depression muscle weakness nightmares body aches sweating nausea vomiting When drug abuse escalates to dependence, treatment becomes complicated. [healthline.com]

  Alcoholism is a disease with four main features: craving - a strong need to drink loss of control - not being able to stop drinking once you've started physical dependence - withdrawal symptoms, such as nausea, sweating, or shakiness when you don't drink [icd9data.com]

  However, THC-based drugs to treat pain and nausea are already FDA approved and prescribed, and scientists continue to investigate the medicinal properties of other chemicals found in the cannabis plant—such as cannabidiol, a non-psychoactive cannabinoid [web.archive.org]

  Feeling sick (nausea) or being sick (vomiting). Diarrhoea. Tremor. Poor sleep. Restlessness. General aches and pains. Just feeling awful. Tolerance is usually a part of dependence. [patient.info]

• Abdominal Pain

  Abdominal pain, nausea, vomiting, and diarrhea are possible. Vomiting blood, or blood in bowel movements, can be life threatening. Withdrawal syndromes are variable depending on the agent but can be life threatening. [emedicinehealth.com]

• Hip Pain

  Low back pain (LBP) occurred in 96 patients, whereas 22 had shoulder pain, 8 had hip pain, and 77 had knee pain. Patients were divided into drug dependence and nondrug dependence groups based on the Severity of Dependence Scale (SDS) scores. [ncbi.nlm.nih.gov]

• Anhedonia

  Pers Soc Psychol Bull 31:121–135. doi: 10.1177/0146167204271309 PubMed CrossRef Google Scholar Wise RA (1982) Neuroleptics and operant behavior: The anhedonia hypothesis. [doi.org]

  Novelty reward as a measure of anhedonia. Neurosci Biobehav Rev. 2005; 29 :707–714. [ PubMed ] [ Google Scholar ] Bjornebekk A, Mathe AA, Brene S. [ncbi.nlm.nih.gov]

• Denial

  Denial among users was 69.2% and denial among negative self report was 45%. A poor level of agreement (K) was found between results of self-report and urinalysis for all the treatment seekers. [ncbi.nlm.nih.gov]

  Though "denial" used to be considered a symptom of addiction, recent research has shown that people who are addicted have far less denial if they are treated with empathy and respect, rather than told what to do or "confronted." [web.archive.org]

  It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. [icd9data.com]

  Though denial is a common symptom of addiction, people who are addicted have far less denial if they are treated with empathy and respect, rather than told what to do or being confronted. [medlineplus.gov]

  You may be met with excuses, denial or anger. Be prepared to respond with specific examples of behavior that has you worried. Don’t expect the person to stop without help: you have heard it before - promises to cut down, stop - but, it doesn’t work. [psychiatry.org]

• Suicidal Ideation

  Lynskey MT, Glowinski AL, Todorov AA, Bucholz KK, Madden PA, Statham DJ, Martin NG, Heath AC: Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use. [doi.org]

• Irritability

  Central nervous system hyperactivity, mydriasis, tremors, gastrointestinal irritation, and diarrhea are typical for opioid withdrawal, including heroin, while tachycardia, hyperreflexia, confusion, and seizures are reported after cessation of benzodiazepine [symptoma.com]

  As alcohol also irritates the stomach, heavy drinking can cause sickness and nausea, and sometimes diarrhoea. Alcohol also has a dehydrating effect, which is the main reason why excessive drinking can lead to a hangover. [ufs.ac.za]

  […] friends, friends who are known alcohol or drug users Changes in habits at home, loss of interest in family and family activities Can’t pay attention, forgetting things Not motivated to do anything, has no energy or self-esteem Moody, has sudden outbursts, irritated [sfad.org.uk]

  Long-term marijuana users trying to quit report withdrawal symptoms including irritability, sleeplessness, decreased appetite, anxiety, and drug craving, all of which can make it difficult to abstain. [web.archive.org]

  They can have problems going smoothly from sleep to awake states, and often become irritable and cry. Difficulties with reactivity to stimuli. [sheknows.com]

• Headache

  J Headache Pain. 2012 Nov;13(8):653-60. doi: 10.1007/s10194-012-0492-z. Epub 2012 Oct 18. [ncbi.nlm.nih.gov]

  Many people in our society are dependent on caffeine and experience withdrawal symptoms such as headache, fatigue, and difficulty concentrating if they miss their morning cup of coffee 8. [drugabuse.com]

  Headache. So, in effect, the medicine acts as a deterrent for when you are tempted to drink. It can help some people to stay off alcohol. [patient.info]

  The drug can also be chemically synthesized in the laboratory. 6 Users report being in a pleasant dreamlike state that lasts 12–18 hours, although mescaline can cause vomiting, headaches, and a feeling of anxiety. 7.4.4. [journals.lww.com]

• Apathy

  The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study. Psychopharmacology (Berl.) 231, 2251–2259 (2014) 103. von Sydow, K., Lieb, R., Pfister, H., Hofler, M. & Wittchen, H. U. [doi.org]

  Drugs such as cocaine and methamphetamine are associated with severe emotional withdrawal symptoms such as depression and apathy, and people may be at risk for accidents due to issues with judgment during the withdrawal period. 5 Alcoholism Treatment [projectknow.com]

  Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006; 16 :916–928. doi: 10.1093/cercor/bhj043. [ PubMed ] [ CrossRef ] [ Google Scholar ] 122. Goldman-Rakic PS. [ncbi.nlm.nih.gov]

• Agitation

  Alternatively, the person may be agitated, angry, anxious, and unable to sleep. Hallucinations are possible. Abnormal vital signs (temperature, pulse rate, respiratory rate, blood pressure ) are possible and can be life threatening. [emedicinehealth.com]

  As these synthetic cannabinoids cause tachycardia, agitation, and nausea, supportive care will be needed for 8 hours after use. 28 7.4.3. [journals.lww.com]

  Stimulants (including Ritalin, Concerta, Adderall, Dexedrine): Dilated pupils, reduced appetite; agitation, anxiety, irregular heartbeat, high body temperature; insomnia, paranoia. [helpguide.org]

  If you feel relaxed and happy when you are high, then you experience intense anxiety and agitation when you are in withdrawal. You may feel sick when you try to stop using, and you need to keep using to feel normal. [wikihow.com]

  Withdrawal from Meth is associated with disturbed sleep, anxiety, depressed mood, reduced energy and agitation ( McGregor et al., 2005 ). [ncbi.nlm.nih.gov]

• Personality Change

  The release of sympathetically active substances by the use of amphetamines, most commonly 3,4-methylenedioxymethamphetamine (MDMA), can lead to euphoria, aggression, and personality changes. [journals.lww.com]

  Early research raised fears that even occasional puffing on a joint might lead to personality changes, birth defects, brain shrinkage, sterility in men, lowered resistance to disease and heart damage. [druglibrary.org]

• Sexual Dysfunction

  dysfunction F19.182 Other psychoactive substance abuse with psychoactive substance-induced sleep disorder F19.188 Other psychoactive substance abuse with other psychoactive substance-induced disorder F19.19 …… with unspecified psychoactive substance-induced [icd10data.com]

The diagnostic workup must start with a carefully obtained patient history, as only a few questions during the interview may reveal the cause of symptoms and the substance that caused dependence. Physicians must bear in mind that peak dependence rates are during adolescence - Alcohol and marijuana dependence most likely occurs around 17-18 years of age, whereas cocaine abuse peaks around 23-25 years. of age [5]. What is worrisome is that more than 10% of cocaine, marijuana and alcohol users become dependent within the first 10 years of use [5]. These findings further emphasize the importance of a meticulous patient history regarding prior substance use and additional questions that will identify whether diagnostic criteria for dependence can be met [2]. More importantly, information from parents, close relatives or friends may be particularly helpful when there is a suspicion of drug dependence, as the patient may not always disclose such information. If the diagnosis is not confirmed, toxicology testing can be performed for marijuana, cocaine, opioids, amphetamines, phencyclidine, benzodiazepines, barbiturates, and alcohol [2]. Urine is tested most commonly, while blood, saliva, sweat or hair samples can be used as well [2].

1. Gould TJ. Addiction and Cognition. Addict Sci Clin Pract. 2010;5(2):4-14.
2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fifth Edition. Arlington, VA: American Psychiatric Publishing; 2013.
3. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
4. Hasin DS, O’Brien CP, Auriacombe M, et al. DSM-5 Criteria for Substance Use Disorders: Recommendations and Rationale. Am J Psychiatry. 2013;170(8):834-851.
5. Wagner FA, Anthony JC. From first drug use to drug dependence; developmental periods of risk for dependence upon marijuana, cocaine, and alcohol. Neuropsychopharmacology. 2002;26(4):479-488.