Dinesh Sangroula, M.D., Muhammad Ovais, M.D., Fahad Waseem, M.B.B.S.

Abstract
Background: Cocaine is a powerful stimulant that directly affects the brain. It is used by more than 14 million people worldwide. Cocaine accounts for about 13 % of all admissions related to drug abuse in the hospitals. Its use disorder is now a rational for the diagnosis of cocaine abuse and cocaine dependence according to the DSM –V criteria. It is one of the most prevalent public health problems worldwide and the number of users is increasing day by day. Unlike heroin and alcohol, there is no any FDA approved medication for its acute overdose or its chronic use.

Method: Realizing the fact that it is very important to have basic knowledge on its use and about the recent updates on the research for its effects and treatment, we searched various articles through different databases like Pubmed, Embase etc. and many medical journals. We attempt to write this article to spread awareness among the clinicians and the patients and to get a deeper and better understanding about the consequences of cocaine abuse in the general population. We have included relevant history of its use, mechanism of action, pharmacokinetics, epidemiology, risk factors, clinical manifestation and management.
Results: Environmental factors have a strong influence; however genetics play an important role as well. Chronic cocaine use is associated with cognitive impairment affecting visual-motor performance, attention, verbal memory, risk reward decision making, suicidal ideation and suicidal attempts. Chronic use by any route of administration is associated with increased risk of infection, especially viral hepatitis, HIV and infection. Cessation results in withdrawal syndrome that has psychological features, but is medically serious. Currently there is no approved medication to treat cocaine addiction. Behavioral therapy is significantly important when it comes to cocaine abuse treatment
Conclusion: Cocaine use has tremendous physical and psychosocial impact on human life. Larger research studies needs to be conducted in future, to learn more about the effective pharmacological treatments with their exact mechanism and doses required.

Introduction
According to 2008 National Survey of Drug Use and Health (NSDUH), there were 1.9 million cocaine users in the US, of which 359,000 were active crack users. Adults between 18 to 25 years of age are among the highest active cocaine users. Rates are higher among males (0.4%) than females (0.1%). Estimated 12 month prevalence in the US is 0.2 % among 12 to 17 years age group and 0.3% among 18 years and older (1). Cocaine is used by more than 14 million people worldwide and is mostly abused among urban men ages between 15 to 35 years (2). About 6 percent of active users in the US are adolescents (3) and is the leading cause of frequent visits of adolescents to the emergency department in US hospitals. Under the Controlled substances act in the United States (US), it is classified as a schedule 2 medication (4). Cocaine also known as “cracks” is one of the most addictive substances used by human beings. Cocaine abuse is one of the most common problems seen in the psychiatric clinical setting in the US (5).

Method
A comprehensive review of published literature was conducted in PubMed, Embase, American Journal of Psychiatry, JAMA psychiatry, Journal of Clinical Psychopharmacology, JAMA Neurology, Addiction (Journal), Journal of Clinical Psychiatry etc. and various medical journals and newspapers. No date restrictions were used. Article relevant to the topic of cocaine abuse were searched. Terms for search included but not limited to “Cocaine Abuse”, Cocaine”, “Cocaine” “Addiction”, “Dependence”, “Cocaine Environment”, “Cocaine Genetics”etc. Selected articles were reviewed to identify additional articles that may have been missed by the keyword search. In total, over 700 articles were initially reviewed, with 600 excluded because of minimal information data on the subject of cocaine abuse.

Discussion
History
Cocaine was originally extracted from the leaf of “Erythroxylum coca bush” that grew in the Andes Mountain region of South America. The name derived from “coca” and alkaloid suffix “ine” formulating its name to cocaine (6).The coca leaves were chewed and ingested for its stimulant effects for thousands of years mainly in South America (Peru and Bolivia being most common). It was in 1859 when a German chemist Albert Niemen, first extracted cocaine alkaloid from coca leaves. In 1880, it was first used as a local anesthetic agent for its vaso-constrictive and analgesic effects and since then, it has been used for eye, nose and throat surgery. Sigmund Freud studied its general pharmacological effects by self-administration and realized its ability to cure depression and sexual impotence in 1884. Furthermore, in 1914 cocaine was classified as a narcotic drug along with morphine and heroin. The coca leaves was found to be an active ingredients of Coca-Cola from 1880 to 1903. In 1922, cocaine was finally removed as an active ingredients and it was no longer considered to be legal (7).
Coca paste is prepared by mixing dried coca leaves in alkaline bases with potassium permanganate, sulfuric acid and a solution of kerosene and gasoline. Cocaine is known by names that reflect both appearance and effects. Coca paste is often called as “base”, “pasta”, “pitallo” and “buscuso”. The powder crystalline form is often referred as “snow” (8).

Risk factors
Cocaine use is common in all socio-economic groups. The highest prevalence is among the unemployed men in their 20’s with underlying psychiatric disorders. Cigarettes smokers and alcoholics are 10 times more likely to abuse cocaine. Among the active cocaine users, 92 percent are alcoholic and 79 percent are smokers. Genetic factors and environmental factors including family, religious and social factors play a strong role in cocaine abuse (8, 9). In females, lifetime risk of developing cocaine use disorders is mainly influenced by genetics risk factors (10, 11).

Mechanism of action
Cocaine increases the level of neurotransmitters like dopamine, norepinehprine and serotonin in the brain. Therefore, also known as triple reuptake inhibiter (TRI), it acts by targeting nucleus accumbens, prefrontal cortex and the dopamine rich ventral segmental area of the brain (12, 13). Chronicity can result in either of the two distinctive pharmacological adaptations; sensitization or tolerance. In animals, sensitization result from low dose exposure while tolerance results from frequent, high-dose or long-term exposure. There is also a significant decrease in dopamine receptors (D2) in the brain of addicted person as compared to non addictive person (14, 15).

Table 1: Effects on specific organ-system

Central Nervous System	Increased risk of cerebrovascular disease, ischemic and hemorrhagic stroke (16), paranoia (17). Cocaine induced psychotics disorder (CIDP) occurs within a month of cocaine intoxication or withdrawal, male, longer duration of cocaine use, iv cocaine etc. (18). Associated with acute dystonic reactions, choreoathetosis, akathisia (so called crack dance) and exacerbation of Tourette’s syndrome (19). Abnormal functioning of striatal dopaminergic system, hypertrophy of striatal structures (20) and exacerbation of migraine (21). In response to stress, CRF (corticotrophin-releasing factor) activates the hypothalamic pituitary –adrenal axis as well as behavioral and immune processes and mediates some of the effects of cocaine (22).
Cardiovascular system	Increased risk of chest pain (14, 23), aortic dissection (15), myocarditis and cardiomyopathy (24), acute coronary syndrome (25). Tachycardia and Hypertension (26). Arrythmogenic effects is medicated by its on K channel (blocking), calcium channel (enhances the function) and stopping the flow of Na channel during depolarization (27).
Respiratory system	Intranasal: chronic rhinitis, perforation of nasal septum and sinusitis. Smoked: shortness of breath, wheezing and asthma exacerbation (25, 28).
Gastrointestinal System	Decrease salivary gland secretions, bruxism (29). Reduced gastric motility, and delayed gastric emptying (25). Gastrointestinal tract ulceration, infarction, perforation and ischemic colitis due to its vaso-constrictive properties (25, 30).
Renal System	Acute renal insufficiency due to interstitial nephritis (31). Rhabdomyolysis is a leading cause of renal failure in cocaine user and can be life threatening (32-35).
Integumentary System	Necrotizing vasculitis, damage to the nasal osseo-cartilaginous structure. Cutaneous vasculitis syndrome by cocaine contaminated with Levamisole (36-38).
Obstretics and gynecology	Vaginal bleeding, abruption placenta, placenta previa, premature membrane rupture, premature birth, low birth weight. Classified as a category C for pregnancy (39-41). Irregular menses in women. Lactation not advised after cocaine administration (42-44).
Eye	Arterial and venous occlusion (39), retinal hemorrhages (40), inflammation of papilla (41) and keratopathy (42). Increases the effects of endothelin -1(43).
Immune System	Associated with HIV by sharing needles and injections (44). Injection risk also increases the transmission of other viruses including HCV and HBV; HCV has a particularly high incidence rate among injection drug users (45).

Pharmacokinetics
Currently, there are two chemical forms of cocaine that are frequently used. The water soluble “hydrochloride salt” and the water insoluble “base or freebase” (alkaloid as in coca leaves). Both of these forms contain same cocaine molecules and exert the same action once they reach the brain and other target organs. Cocaine salt cannot be efficiently smoked as it melts at 195° C. It is readily injected and can be snorted as well. Due to its water soluble nature, it is easy to dissolve making it ideal for absorption through muscles as well as mucous membrane. Cocaine base (crack) can be smoked because it has a relatively low melting point 98° C (3, 6).

Cocaine is readily absorbed through the mucous membranes of the nose, mouth and from the genitourinary, gastrointestinal and respiratory. Passive absorption may occur through intact skin or by inhalation of second hand smoke. Such passive exposure can cause adverse effects in infants. It is readily taken up by the body parts such as heart, kidney, adrenal glands and liver. Cocaine appears in blood, urine, hair, sweat, saliva and breast milk. It crosses the placenta and be detected in meconium of newborn if mother has recently used cocaine (16-21, 49-52).
It is mainly metabolized by the liver to benzoylecgonine (95%) and to ecgonine (5%) by cytochrome P450 microtonal enzyme system. Intravenous injection has a100% bioavailability with an onset of action within 30 seconds. Duration of action varies from between 10 to 30 minutes. Inhaled administration can result in onset within seconds. This route is fastest in action and reaches the peak level in the blood within no time. Intranasal and gastrointestinal administration cause slower onset and the activity begin within 3 to 5 minutes. The blood levels peaks at in about 10 to 20 minutes and action starts fading in 45 minutes to 60 minutes respectively. Oral absorption results in a slower onset and it takes about 10 to 15 minutes to reach the level of 30 to 50 mg/dl, and it reaches the peak level (160 ng/ml) in about 60 minutes (4, 8).

Clinical Manifestations
The clinical manifestation of cocaine use depends on the dose of cocaine the minimum toxic dose varies depending upon the route of administration. Toxic doses can range 12-15 mg when ingested orally, 20-100mg intranasal and 50—200 mg smoked (8). Table 2 summarizes the important signs and symptoms of cocaine intoxication and withdrawal.

Table 2: Signs and symptoms of cocaine use (8):

Signs and symptoms of cocaine intoxication	Signs and symptoms of cocaine withdrawal
Euphoria, high energy level, talkativeness Insomnia, Decreased appetite Mood swings, Aggression, hyperactivity, restlessness Paranoia, Psychosis Cocaine Bugs(tactile hallucination) Pupil dilatation Cognitive impairment Hyperpyerxia, Confusion, Seizures, Coma HTN, Cardiac Arrhythmia, Non obstructive MI, Stroke, Sudden cardiac arrest	Dysphoria Depression Anxiety Increased appetite and weight gain Insomnia/hypersomnia Fatigue, Anhedonia Compulsive craving Unpleasant withdrawal (may have suicidal ideation)

Diagnosis
The diagnosis of cocaine use disorder is based on the history of, obtained primarily from the patient and from collateral sources (e.g. friends, familial, and medical records) when available.

Benzoylecgonine is typically used for the diagnosis. It is present in urine for 1-3 days after a single dose and for 7-12 days in individuals who used cocaine repeatedly.

Treatment
A. Treatment of acute overdose of cocaine (4, 55)
Unlike benzodiazepine and opioids, there is no specific antidote for acute cocaine overdose. Management is symptomatic depending upon the amount of drug overdosed and the manifestation of the symptoms and signs.
1. Initial assessment and stabilization of airway, breathing and circulation is followed by detailed clinical evaluation, monitoring of vitals, cardiac monitor, intra venous access, pulse oximetry, oxygen, EKG, routine emergency labs including urine for toxicology and pregnancy test .
2. Close monitoring of temperature and steps to prevent hyperthermia and subsequent rhabdomyolysis using cooling blankets and tepid water
3. Avoid physical restraints as much as possible. Benzodiazepine is used as pharmacological restraints, seizure prophylaxis and to decrease cardiovascular symptoms.
4. Patient may be observed in ER until symptoms subside or admitted, or followed up in an outpatient settings including referral to psychosocial intervention.

B. Treatment of Cocaine dependence
Pharmacotherapy
Unlike heroin and alcohol, there is no FDA approved medication to treat chronic dependence of cocaine. Vigabatrin, Modafinil, Tiagibine, Disulfiram, Lamotrigine and Topiramate have shown promising results in control trials. Disulfiram has been found to be most consistent in reducing abuse affects. Morning dose Modafinil has shown to promote nocturnal sleep, normalizes sleep architecture and decreases daytime sleepiness in abstinent cocaine users and Lamotrigine to reduce craving and depressive symptoms in cocaine dependents (43, 44).

Psychostimulants have been found to be effective in studies but their abuse potential has limited their use in practice. Many other medication have been tried in the research studies like Bupropion, Amantadine, antidepressants etc, but none of them has been affirmed to be fully effective and safe to be used in clinical practice which entails the need of larger studies in future.

Behavioral therapy
Behavioral therapy offers cocaine-addicted patients consistency management or motivational incentive. It’s an incentive based program that utilizes rewarding strategy for patients successful in abstaining from cocaine and other addictive drugs (53).

Cognitive behavior therapy
This therapy is utilized for cocaine relapse. This also aids in cocaine –addictive individuals to abstain –from cocaine and other substance abusers. In one of the studies it shows that CBT4CBT is helpful in cocaine dependent individuals enrolled in methadone maintenance program (54).

Therapeutics communities (TCS) or residential programs
TCS usually require a 6 to 12 months of stay and use the program entire community as active components of the treatment.

Cocaine anonymous
Community based recovery groups such as cocaine anonymous is a 12 step program and has shown promising results for people trying to sustain cocaine abstinence (55).

Others
Individual therapy, family therapy, group therapy, reward therapy are other modalities. In general, the treatment should be focused on the patient need. For example, patient with unemployment should be provided with vocational rehabilitation and career counseling, patient with marital problems should be offered couple counseling (4).

Conclusion
Cocaine use is most prevalent in North and South America, and increasingly in Western Europe, especially among urban men aged 15 to 35 years. It is the illegal drug most often associated with emergency department visits in the US. Abuse liability is greater with intravenous and smoked cocaine, compared to intranasal and oral use.

Drug testing detects the metabolite benzoylecgonine, which is usually detectable two to four days after the last cocaine use, although this can be up to 14 days after heavy, prolonged use.

Cocaine use increases energy and alertness, can produce euphoria, and decreases appetite and need for sleep. Adverse effects may include anxiety, irritability, paranoia, delusions, and hallucinations. These may be accompanied by tachycardia, diaphoresis, nausea, and pupil dilatation. There is poor correlation between cocaine plasma concentrations and toxicity. Withdrawal symptoms from chronic cocaine use are predominantly psychological: depression, anxiety, anhedonia, cocaine craving, and increased sleep. Most symptoms are self limited and resolve within one to two weeks.

In summary, cocaine use has tremendous physical and psychosocial impact on human life. We need to develop an effective modality of treatment focusing more on the effective drugs. Future research should focus more on establishing the exact mechanism of action of the proposed medication. Larger research studies needs to be conducted in future for drugs to prove their effectiveness with minimal side effects.

References
(1) Hatsukami, D., & Fischman, M. (1996). Crack cocaine and cocaine hydrochloride: Are they different myth or reality? JAMA, 279(19), 1580-8.
(2) 2007 world drug report. (2007). Vienna: United Nations Office on Drugs and Crime.
(3) Drug Abuse Warning Network, 2005: National Estimates of Drug-Related Emergency Department Visits. (n.d.). PsycEXTRA Dataset.
(4) Diagnostic and statistical manual of mental disorders: DSM-5. (5th ed.). (2013). Washington, D.C.: American Psychiatric Association.
(5) Substance Abuse and Mental Health Services Administration. (2007). Choice Reviews Online.
(6) Karch, S. (2006). A brief history of cocaine: From Inca monarchs to Cali cartels : 500 years of cocaine dealing (2nd ed.). Boca Raton, FL: CRC/Taylor & Francis.
(7) Sadock, B., & Kaplan, H. (2007). Kaplan & Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry. (10th ed.). Philadelphia: Wolter Kluwer/Lippincott Williams & Wilkins.
(8) Harper, SJ., & Jones, NS. (2006). Cocaine: What role does it have in current ENT practice? A review of the current literature. The Journal of Laryngology & Otology, 120(10), 808-811.
(9) Kendler, K., Myers, J., & Prescott, C. (2007). Specificity of Genetic and Environmental Risk Factors for Symptoms of Cannabis, Cocaine, Alcohol, Caffeine, and Nicotine Dependence. Arch Gen Psychiatry Archives of General Psychiatry, 1313-1313.
(10) Stevens, D. (1999). Genetic risk factors influenced cocaine abuse and dependence more than cocaine use in women. Evidence-Based Mental Health, 63-63.
(11) Kendler, K., & Prescott, C. (1998). Cocaine use, abuse and dependence in a population-based sample of female twins. The British Journal of Psychiatry, 345-350.
(12) Rothman, R., Baumann, M., Dersch, C., Romero, D., Rice, K., Carroll, F., & Partilla, J. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse, 39(1), 32-41.
(13) Howell, L., & Kimmel, H. (2008). Monoamine transporters and psychostimulant addiction. Biochem Pharmacol, 75(1), 196-207.
(14) Koob, G. (1996). Drug Addiction: The Yin and Yang of Hedonic Homeostasis. Neuron, 893-896.
(15) Schenk, S., & Partridge, B. (1997). Sensitization and Tolerance in Psychostimulant Self-Administration. Pharmacology Biochemistry and Behavior, 543-550.
(16) Follador, M., Yonamine, M., Moreau, R., & Silva, O. (2004). Detection of cocaine and coca ethylene in sweat by solid-phase microextraction and gas chromatography/mass spectrometry. Journal of Chromatography B, 811(1), 37-40.
(17) Pil, K., & Verstraete, A. (2008). Current Developments in Drug Testing in Oral Fluid. Therapeutic Drug Monitoring, 196-202.
(18) Bernshaw, N. (2002). Website Review: American Academy of Pediatrics, Committee on Drugs: The Transfer of Drugs and Other Chemicals Into Human Milk. Journal of Human Lactation, 81-82.
(19) Nice, F., Snyder, J., & Kotansky, B. (2000). Review: Breastfeeding and Over-the-Counter Medications. Journal of Human Lactation, 319-331.
(20) Ostrea, E. (1999). Testing for exposure to illicit drugs and other agents in the neonate: A review of laboratory methods and the role of meconium analysis. Current Problems in Pediatrics, 41-56.
(21) Angrist, B., & Sudilovsky, A. (1987). Central Nervous System Stimulants: Historical Aspects and Clinical Effects. Stimulants, 99-165.
(22) Baselt, R. (2001). Drug effects on psychomotor performance. Foster City, Calif.: Biomedical Publications.
(23) Fischman, M., & Foltin, R. (1998). Cocaine Self-Administration Research. Cocaine Abuse, 181-207.
(24) Boghdadi, M., & Henning, R. (1997). Cocaine: Pathophysiology and clinical toxicology. Heart & Lung: The Journal of Acute and Critical Care, 466-483.
(25) Brust, J. (1998). Acute Neurologic Complications Of Drug And Alcohol Abuse. Neurologic Clinics, 503-519.
(26) Neiman, J., Haapaniemi, H., & Hillbom, M. (2000). Neurological complications of drug abuse: Pathophysiological mechanisms. European Journal of Neurology, 595-606.
(27) Moran, M. (2011). Study Illuminates Cocaine’s Direct Effect on Cognition. Psychiatric News PN, 19-19.
(28) Afonso, L., Mohammad, T., & Thatai, D. (2007). Crack Whips the Heart: A Review of the Cardiovascular Toxicity of Cocaine. The American Journal of Cardiology, 1040-1043.
(29) Qureshi, A., Suri, M., Guterman, L., & Hopkins, L. (2001). Cocaine Use and the Likelihood of Nonfatal Myocardial Infarction and Stroke : Data From the Third National Health and Nutrition Examination Survey. Circulation, 502-506.
(30) Carlin, N., Nguyen, N., & Depasquale, J. (2014). Multiple Gastrointestinal Complications of Crack Cocaine Abuse. Case Reports in Medicine, 1-3.
(31) Alvarez-Cordovés, MM., Mirpuri-Mirpuri, PG., & Pérez-Monje, AJ. (2012). [Rhabdomyolysis associated with cocaine use]. Semergen, 38(2), 102-6.
(32) Alfaro, R., Vasavada, N., Paueksakon, P., Hernandez, G., & Aronoff, G. (2013). Cocaine-induced acute interstitial nephritis: A case report and review of the literature. J Nephropathol, 2(3), 204-9. doi:10.12860/JNP.2013.33
(33) De Mendoza Asensi, D., Rodríguez Jornet, A., Carvajal Díaz, A., Andreu Navarro, FJ., Sala Rodó, M., Cervantes García, M. (2004). Acute renal insufficiency associated to cocaine consumption. Rev Clin Esp, 204(4), 206-11
(34) Jiménez-Gallo, D., Albarrán-Planelles, C., Linares-Barrios, M., García-Moreno, E., de la Varga-Martínez, R., Rodríguez-Hernández, C. (2014) Necrotizing vasculitis induced by cocaine. Rev Clin Esp, 214(5), 51-53. doi: 10.1016/j.rce.2014.01.008
(35) Van der Poel, NA., Schot, LJ., Menger, DJ. (2013). Local complications of intranasal cocaine abuse: diagnostic and therapeutic guidelines. Ned Tijdschr Geneeskd, 157(24), A6035
(36) Souied, O., Baydoun, H., Ghandour, Z., & Mobarakai, N. (2014). Levamisole-Contaminated Cocaine: An Emergent Cause of Vasculitis and Skin Necrosis. Case Reports in Medicine, 1-3.
(37) Denegri, A., Ameri, P., Paparo, F., & Murialdo, G. (2014). Lower limb ischemia due to long-term abuse of cocaine. Journal of Cardiovascular Medicine, 1-1.
(38) Chiriboga, C. (2003). Fetal Alcohol and Drug Effects. The Neurologist, 267-279.
(39) Kuczkowski, K. (2007). The effects of drug abuse on pregnancy. Current Opinion in Obstetrics and Gynecology, 578-585.
(40) Palha, A., & Esteves, M. (2008). Drugs of Abuse and Sexual Functioning. Sexual Dysfunction Advances in Psychosomatic Medicine, 131-149.
(41) Carey, J. (2006). Pharmacological Effects On Sexual Function. Obstetrics and Gynecology Clinics of North America, 599-620.
(42) Bernshaw, N. (2002). Website Review: American Academy of Pediatrics, Committee on Drugs: The Transfer of Drugs and Other Chemicals Into Human Milk. Journal of Human Lactation, 81-82.
(43) Nice, F., Snyder, J., & Kotansky, B. (2000). Review: Breastfeeding and Over-the-Counter Medications. Journal of Human Lactation, 319-331.
(44) Morgan, P., Pace-Schott, E., Pittman, B., Stickgold, R., & Malison, R. (2010). Normalizing Effects of Modafinil on Sleep in Chronic Cocaine Users. AJP American Journal of Psychiatry, 167(3), 331-340.
(45) Pavlovic, Z. (2011). Lamotrigine Reduces Craving and Depressive Symptoms in Cocaine Dependence. Journal of Neuropsychiatry and clinical Neuroscience, 23(1), E32. doi: 10.1176/appi.neuropsych.23.1.E32.
(46) Cone, E., Yousefnejad, D., Hillsgrove, M., Holicky, B., & Darwin, W. (1995). Passive Inhalation of Cocaine. Journal of Analytical Toxicology, 399-411.
(47) Kavanagh, KT., Maijub, AG., Brown, JR. (1992). Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests. Otolaryngology Head Neck Surg,107:363
(48) Le, SD., Taylor, RW., Vidal, D., Lovas, JJ., Ting, E. (1992). Occupational exposure to cocaine involving crime lab personnel. J Forensic Sci, 37(4), 959-68.
(49) Mott, SH., Packer, RJ., Soldin, SJ (1994). Neurologic manifestations of cocaine exposure in childhood. Pediatrics, 93(4), 557-560.
(50) Mirchandani, HG., Mirchandani, IH., Hellman, F. Passive inhalation of free-base cocaine (‘crack’) smoke by infants. Arch Pathol Lab Med, 115:494.
(51) Fowler, J., Volkow, N., Wang, G., Gatley, S., & Logan, J. (2001). [11]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy. Nuclear Medicine and Biology, 561-572.
(52) Musshoff, F., Driever, F., Lachenmeier, K., Lachenmeier, D., Banger, M., & Madea, B. (2006). Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests. Forensic Science International, 118-123.
(53) Kampman, K. (2000). Amantadine treatment for cocaine-dependent patients with severe withdrawal symptoms. Expert Review of Neurotherapeutics, 601-608.
(54) Carroll, K., Kiluk, B., Nich, C., Gordon, M., Portnoy, G., Marino, D., & Ball, S. (2014). Computer-Assisted Delivery of Cognitive-Behavioral Therapy: Efficacy and Durability of CBT4CBT Among Cocaine-Dependent Individuals Maintained on Methadone. AJP American Journal of Psychiatry, 436-444.
(55) National Institute on Drug Abuse. Cocaine Retrieved from: http://www.drugabuse.gov/drugs-abuse/cocaine on July 6, 2014.

Affiliations:
Dinesh Sangroula, M.D.: North Shore – LIJ, Zucker Hillside Hospital, NY, USA
Muhammad Ovais, M.D.: St Louis University, St Louis, MO, USA
Fahad Waseem, M.B.B.S.: M.S. Hospital, Karachi, Pakistan

Correspondence: Dinesh Sangroula, M.D., North Shore – LIJ, Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, USA.