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Benzphetamine

Benzphetamine is a sympathomimetic amine with pharmacological properties similar to amphetamines, primarily used as a short-term adjunct in the management of exogenous obesity through appetite suppression, in combination with a reduced-calorie diet and increased physical activity.^[1]^[2] Available as generic the hydrochloride salt in 25 mg and 50 mg oral tablets, it was approved by the U.S. Food and Drug Administration in 1960 for patients aged 12 years and older with a body mass index of 30 kg/m² or greater who have not responded to appropriate non-drug interventions.^[2]^[3] As a Schedule III controlled substance under the Controlled Substances Act, benzphetamine carries a moderate potential for physical and psychological dependence, necessitating strict prescription controls.^[4] The mechanism of action involves binding to adrenergic receptors in the central nervous system, particularly in the hypothalamic feeding center, which promotes the release of norepinephrine and dopamine to reduce hunger and increase metabolic rate.^[1]^[2] It is metabolized in the liver to active metabolites, including amphetamine and methamphetamine, with a half-life ranging from 16 to 31 hours and protein binding of 75-99%.^[1] Clinical studies indicate modest weight loss, typically a fraction of a pound per week, with the greatest effects occurring in the initial treatment weeks, though tolerance may develop over time.^[2] Despite its efficacy in short-term use (generally a few weeks), benzphetamine is associated with significant risks, including cardiovascular effects such as palpitations, tachycardia, and elevated blood pressure, as well as central nervous system overstimulation manifesting as restlessness, insomnia, dizziness, and euphoria.^[5]^[2] Prolonged use beyond three months has been linked to serious adverse events like primary pulmonary hypertension (with a 23-fold increased risk) and valvular heart disease, prompting recommendations to discontinue therapy if weight loss is less than 4 pounds after four weeks.^[2] Contraindications include advanced arteriosclerosis, symptomatic cardiovascular disease, hyperthyroidism, glaucoma, and concurrent use with monoamine oxidase inhibitors, with precautions advised for patients with a history of drug abuse or psychiatric disorders.^[2]^[5]

Medical use

Indications

Benzphetamine is indicated for the short-term (a few weeks) management of exogenous obesity as an adjunct to caloric restriction as part of a weight reduction regimen that includes appropriate diet and exercise.^[2] It is specifically approved for use in patients aged 12 years and older with an initial body mass index (BMI) of ≥30 kg/m² who have not achieved adequate weight loss through non-pharmacologic measures alone, such as diet and physical activity.^[2] Patient selection emphasizes those for whom alternative weight management strategies have failed, and it is not intended for cosmetic weight reduction or long-term therapy, as tolerance to its appetite-suppressing effects typically develops over time, limiting sustained efficacy.^[2] In clinical trials, benzphetamine has demonstrated modest weight loss when combined with dietary restriction, with patients achieving an average additional reduction of approximately 2.5–3.3 kg compared to placebo over 12–17 weeks.^[6]^[7] However, weight loss plateaus after initial weeks, and most patients experience rebound weight gain to baseline levels upon discontinuation, underscoring the need for ongoing lifestyle interventions.^[2] Use is not recommended in children under 12 years due to lack of established safety and efficacy data in pediatric populations.^[2]

Dosage and administration

Benzphetamine is available in oral tablet form in strengths of 25 mg and 50 mg.^[8] The recommended initial dose for adults is 25 to 50 mg administered once daily, preferably in the mid-morning or mid-afternoon, depending on the patient's eating habits.^[8] Dosage should be individualized based on patient response and tolerance, with subsequent adjustments increasing the dose or frequency up to 25 to 50 mg one to three times daily, not exceeding a maximum of 150 mg per day.^[8]^[2] For elderly patients, dose selection should be cautious, typically starting at the lower end of the dosing range (25 mg once daily) due to the potential for decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy.^[2] In patients with renal impairment, no specific dosage adjustments are required, but caution is advised with close monitoring for adverse effects, as clearance may be altered.^[9] Doses should be titrated gradually based on efficacy and tolerability to minimize risks such as cardiovascular effects.^[10] Tablets should be swallowed whole with water and not crushed, chewed, or broken to ensure proper release and avoid potential overdose.^[2] Administration early in the day is preferred to reduce the risk of insomnia from its stimulant properties.^[11] Treatment should be discontinued if tolerance develops or if there is no satisfactory weight loss (at least 4 pounds) after 4 weeks of therapy at the maximum tolerated dose.^[8] During therapy, patients require regular monitoring, including blood pressure and heart rate assessments at each visit, weight tracking to evaluate progress, and evaluation for signs of dependence or abuse every 2 to 4 weeks given its Schedule III controlled substance status.^[5]^[10] Baseline cardiac evaluation is recommended, with ongoing checks for symptoms of pulmonary hypertension or valvular heart disease.^[2]

Adverse effects

Common side effects

Common side effects of benzphetamine, stemming from its central nervous system stimulant properties, frequently include overstimulation, restlessness, dizziness, insomnia, tremor, sweating, headache, dryness of the mouth, unpleasant taste, nausea, diarrhea, and other gastrointestinal disturbances.^[2] Additional commonly reported effects encompass agitation, anxiety, confusion, irritability, nervousness, mood changes, and trouble sleeping.^[12] These adverse reactions typically manifest within the first week of treatment initiation and are generally mild and reversible.^[13] Many resolve spontaneously with continued use due to the development of tolerance or tachyphylaxis, or through dose reduction; however, some may persist if the dosage exceeds recommended levels, such as greater than 100 mg per day.^[2] Management of these effects focuses on supportive measures tailored to the symptom. For dry mouth, increasing fluid intake or using sugar-free lozenges can provide relief. Insomnia may improve with adherence to sleep hygiene practices, such as avoiding late-day dosing and maintaining a consistent bedtime routine. Gastrointestinal issues like constipation or diarrhea can be addressed by incorporating dietary fiber and ensuring adequate hydration.^[12] Patients should report any persistent or bothersome side effects to their healthcare provider promptly, as adjustments may be necessary to continue therapy effectively.^[13]

Serious adverse effects

Benzphetamine, like other anorectic agents, carries significant cardiovascular risks, particularly with prolonged use. It can cause tachycardia, palpitations, and elevations in blood pressure, which may exacerbate hypertension in susceptible individuals. More severe complications include primary pulmonary hypertension, a rare but potentially fatal disorder associated with anorectic drugs; epidemiological studies indicate a 23-fold increased risk with use exceeding three months. Valvular heart disease has been reported with similar sympathomimetic agents, such as fenfluramine, though no cases have been specifically linked to benzphetamine monotherapy; the FDA recommends baseline cardiac evaluation to detect pre-existing valvular issues or pulmonary hypertension before initiation. Isolated reports also describe cardiomyopathy and ischemic cardiac events, including potential myocardial infarction, in patients with chronic use or predisposing factors. Psychiatric adverse effects are infrequent but can be profound, especially in overdose or extended therapy. Rare instances of psychosis, including hallucinations and mania-like states, have occurred even at recommended doses, potentially resembling schizophrenia with chronic intoxication. Benzphetamine is a Schedule III controlled substance due to its potential for psychological dependence and abuse, leading to severe social dysfunction; abrupt withdrawal after high-dose use may precipitate extreme fatigue, mental depression, and changes in sleep patterns. Other serious reactions encompass stroke in patients with cardiovascular risk factors and severe overdose manifestations. Overdose symptoms include restlessness, tremor, confusion, arrhythmias, fluctuating blood pressure, hyperpyrexia, rhabdomyolysis, seizures, and coma, with fatalities possible from acute poisoning. These events are rare, though the risk escalates in those with comorbidities or concurrent stimulant use.

Contraindications and precautions

Contraindications

Benzphetamine is contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension (systolic >140 mmHg or diastolic >90 mmHg), hyperthyroidism, glaucoma, known hypersensitivity or idiosyncrasy to sympathomimetic amines, agitated states, or a history of drug abuse.^[2] It is also absolutely contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors (MAOIs), due to the risk of hypertensive crisis.^[2] Additionally, benzphetamine should not be used concomitantly with other central nervous system (CNS) stimulants.^[2] Use during pregnancy is contraindicated due to risks of fetal harm, including teratogenicity and embryotoxicity observed in animal studies.^[2] Relative contraindications include mild hypertension, a history of psychosis, and Tourette's syndrome.^[2]^[14] Caution is advised in elderly patients owing to increased risks of falls and age-related declines in organ function that may heighten adverse effects.^[14] These contraindications stem from benzphetamine's sympathomimetic properties, which can exacerbate underlying conditions through elevated blood pressure, potential hypertensive crises, or cardiac events; in glaucoma, the drug may increase intraocular pressure via mydriasis.^[2]^[15] Prior to initiating therapy, screening should include a baseline electrocardiogram (ECG) and blood pressure measurement; treatment must not be started if any absolute contraindication is present.^[2]^[15]

Drug interactions

Benzphetamine, a sympathomimetic amine, exhibits significant drug interactions primarily due to its effects on monoamine neurotransmitters and cardiovascular parameters. Major interactions include those with monoamine oxidase inhibitors (MAOIs) such as selegiline, which can precipitate hypertensive crises through enhanced catecholamine release; concurrent use or administration within 14 days is contraindicated.^[2] Similarly, co-administration with serotonergic drugs like selective serotonin reuptake inhibitors (SSRIs) may potentiate the pharmacologic response to benzphetamine, increasing risks of jitteriness, nervousness, anxiety, restlessness, and racing thoughts.^[16] Sympathomimetics, including pseudoephedrine, amplify central nervous system (CNS) stimulation, potentially leading to excessive sympathomimetic effects such as tachycardia and hypertension.^[5] Moderate interactions involve antihypertensives like beta-blockers, where benzphetamine may counteract their hypotensive effects by stimulating norepinephrine release, necessitating blood pressure monitoring and possible dose adjustments.^[2] Inhibitors of CYP2B6, such as clopidogrel—a minor metabolic pathway for benzphetamine—can prolong its half-life by impeding N-demethylation, thereby increasing exposure and adverse effects.^[1] Alcohol consumption exacerbates CNS depression and cardiovascular risks, including elevated heart rate and blood pressure changes, advising caution or avoidance during therapy. Minor interactions encompass urinary acidifying agents like ascorbic acid, which reduce benzphetamine absorption by promoting renal excretion, potentially diminishing efficacy.^[2] Comprehensive databases report 234 known drug interactions for benzphetamine, alongside 15 disease-related interactions and 3 involving alcohol or food, underscoring the need for thorough prescriber review.^[17] Management strategies generally include avoidance of high-risk combinations, dose modifications for moderate interactions, and vigilant monitoring of blood pressure when co-administered with stimulants or antihypertensives.^[10]

Pharmacology

Pharmacodynamics

Benzphetamine is an indirect-acting sympathomimetic amine with pharmacological activity similar to amphetamines, primarily exerting its anorectic effects through central nervous system stimulation. It promotes the release of catecholamines, particularly norepinephrine from presynaptic neurons, and to a lesser extent dopamine, in the lateral hypothalamic feeding center, thereby suppressing appetite by enhancing satiety signals.^[1]^[9] This neurotransmitter release occurs via reversal of the synaptic vesicular amine transporter (VMAT2), which facilitates the efflux of amines from storage vesicles into the cytoplasm and subsequently into the synaptic cleft. Additionally, benzphetamine inhibits the sodium-dependent dopamine transporter (DAT), further elevating extracellular dopamine levels in the central nervous system.^[1]^[18] The drug also acts as an agonist at alpha-1A and alpha-2A adrenergic receptors, contributing to its sympathomimetic effects, including mild central stimulation and modest elevations in blood pressure. Unlike serotonergic agents such as fenfluramine, benzphetamine does not significantly promote serotonin release, focusing its activity on noradrenergic and dopaminergic pathways. This distinction limits its impact on serotonergic-mediated side effects while targeting catecholamine-dependent appetite regulation.^[1]^[19] As a prodrug, benzphetamine undergoes hepatic metabolism to active metabolites, including amphetamine and methamphetamine, which contribute substantially to its overall pharmacological profile and duration of action. Tolerance and tachyphylaxis develop rapidly with repeated use, typically within weeks, limiting long-term efficacy; this is attributed to downregulation of adrenergic receptors and adaptations in monoamine systems, though the exact mechanisms remain incompletely elucidated.^[1]^[20]^[2] In preclinical studies using rodent models, benzphetamine reduces food intake through central catecholamine modulation, with effects potentiated by interactions such as caffeine co-administration, though specific quantitative reductions vary by dose and model. Benzphetamine does not significantly alter basal metabolic rate or nitrogen excretion, emphasizing its primary role in appetite suppression over direct thermogenic mechanisms.^[21]^[9]

Pharmacokinetics

Benzphetamine is rapidly absorbed from the gastrointestinal tract following oral administration, with peak plasma concentrations typically occurring within 1 to 3 hours post-dose.^[22] The drug exhibits high oral bioavailability, allowing for effective systemic exposure. Pharmacokinetic data in humans are not available, with much information derived from animal studies or related compounds.^[2] Once absorbed, benzphetamine is widely distributed throughout the body, with a volume of distribution averaging 5 L/kg.^[22] It is highly lipid-soluble and readily crosses the blood-brain barrier, facilitating its central nervous system effects.^[22] Plasma protein binding ranges from 75% to 99%.^[1] Benzphetamine undergoes extensive hepatic metabolism primarily via cytochrome P450 2B6, yielding active metabolites including d-methamphetamine and d-amphetamine.^[1]^[20] These metabolites undergo further demethylation and hydroxylation to form compounds such as p-hydroxyamphetamine.^[23] Elimination of benzphetamine occurs mainly through renal excretion of metabolites, with only 5% to 30% of the parent drug excreted unchanged in the urine over 24 hours; this fraction is highly dependent on urinary pH, increasing under acidic conditions.^[10] The elimination half-life of the parent compound is approximately 4 to 5 hours, while the active metabolites amphetamine and methamphetamine have half-lives of approximately 10 hours and 12 hours, respectively (pH-dependent).^[24]^[25]^[26]

Chemistry

Chemical structure and properties

Benzphetamine, chemically known as (2S)-N-benzyl-N-methyl-1-phenylpropan-2-amine, is a synthetic derivative of amphetamine featuring N-methyl and N-benzyl substitutions on the amino group. Its molecular formula is C₁₇H₂₁N, with a molar mass of 239.36 g/mol. The molecule possesses a chiral center at the C2 position adjacent to the nitrogen atom, and the biologically active form is the dextro (S)-enantiomer.^[27] It is typically administered as the hydrochloride salt to enhance stability and solubility. The hydrochloride salt of benzphetamine appears as a white crystalline powder.^[2] It has a melting point of 129–130 °C.^[1] The compound is readily soluble in water and 95% ethanol, with the base form also soluble in organic solvents such as methanol, chloroform, acetone, ether, and benzene.^[2] Its calculated octanol-water partition coefficient (logP) is 4.1, reflecting moderate lipophilicity that facilitates penetration into the central nervous system.^[28] For stability, benzphetamine hydrochloride is stored in tight containers at controlled room temperature (15–30 °C) to maintain integrity.

Synthesis

Benzphetamine was first synthesized through N-alkylation of d-desoxyephedrine hydrochloride (also known as dextromethamphetamine hydrochloride) with benzyl chloride. The process, patented by The Upjohn Company in 1957, involves liberating the free base of d-desoxyephedrine by treatment with sodium hydroxide, followed by reaction with benzyl chloride in the presence of anhydrous sodium carbonate at 120°C for 2 hours. The mixture is then extracted with benzene, the solvent distilled, and the residue fractionally distilled under reduced pressure (127°C at 0.2 mmHg) to isolate the free base. The hydrochloride salt is formed by dissolving the base in ethyl acetate and adding ethanolic hydrogen chloride, yielding white crystals with a melting point of 129–130°C. This method preserves the (S)-configuration at the chiral center, as the starting material is the enantiopure (S)-enantiomer.^[29] A scalable industrial process for benzphetamine hydrochloride, developed by Emcure Pharmaceuticals and published in 2011, improves upon the original by conducting the N-alkylation in an aqueous medium to enhance safety and efficiency under good manufacturing practice (GMP) conditions. Methamphetamine hydrochloride is reacted with benzyl chloride (1.1 equivalents) in water at 75±2°C, using potassium carbonate (3.0 equivalents) as a mild base to facilitate the reaction over several hours. The reaction mixture is cooled, extracted with toluene to isolate the free base, which is concentrated under vacuum, and then converted to the hydrochloride salt by treatment with 10% HCl in ethyl acetate at 10–15°C. The salt is crystallized directly from the mixture without additional purification steps, resulting in >99% purity by HPLC and effective control of impurities such as unreacted methamphetamine. This process is optimized for large-scale production and avoids organic solvents during the alkylation step to minimize environmental impact.^[30] Enantioselective routes to (S)-benzphetamine have been explored to bypass reliance on controlled precursors like methamphetamine. One such method, reported in 2015, employs electrophilic azidation of chiral imide enolates derived from an achiral phenylacetone equivalent, followed by reduction of the azide to the primary amine, N-benzylation with benzyl bromide, and N-methylation via reductive amination with formaldehyde and sodium cyanoborohydride. Key conditions include lithium hexamethyldisilazide for enolate formation at -78°C and diphenyl phosphoryl azide as the azidating agent, achieving >99% enantiomeric excess for the (S)-configuration. The overall yield for the sequence exceeds 40% over five steps, with final purification of the hydrochloride salt via HPLC or recrystallization to >98% purity. This approach maintains stereochemical integrity without racemization and supports scalable synthesis for pharmaceutical applications.^[31] Benzphetamine hydrochloride for commercial use, such as in the brand Didrex, has been manufactured by Pharmacia & Upjohn Company (a subsidiary of Pfizer Inc.) at facilities compliant with GMP standards. Recent patents, including a 2010 application for high-purity crystalline forms (US 2010/0113831 A1), emphasize crystallization techniques from ethyl acetate or isopropanol to further reduce impurities and improve stability, enabling yields of 70–80% in the final salt formation while meeting regulatory requirements for anorectic agents.^[32]^[28]

History

Development

Benzphetamine was developed in the early 1950s by chemists Richard V. Heinzelman and Brooke D. Aspergren at the Upjohn Company in Kalamazoo, Michigan, as part of an extensive search for amphetamine analogs intended to serve as safer anorectics.^[29] The compound, chemically known as N-benzyl-N,α-dimethylphenethylamine, emerged from efforts to modify the amphetamine structure to preserve appetite-suppressing effects while minimizing risks associated with traditional amphetamines, such as high abuse liability and excessive central nervous system stimulation. This work was prompted by growing public health concerns over obesity in the post-World War II era, when dietary habits and sedentary lifestyles contributed to rising prevalence, and amphetamines were widely prescribed for short-term weight management despite their addictive potential.^[33] Pharmaceutical researchers, including those at Upjohn, aimed to engineer derivatives that could support caloric restriction regimens without the pronounced euphoric or hyperstimulant side effects that limited broader clinical adoption of parent compounds like dextroamphetamine. Preclinical evaluations in animal models confirmed benzphetamine's anorexigenic activity, revealing it to be roughly one-third as potent as d-amphetamine in suppressing food intake over chronic dosing periods but approximately one-eighth as stimulating on motor activity in mice, suggesting a reduced propensity for central excitation.^[34] These findings established an initial characterization of the drug's profile, highlighting its potential as a balanced sympathomimetic for obesity treatment.^[34] The core synthesis and pharmacological groundwork were documented in US Patent 2,789,138, filed on June 2, 1952, and granted on April 16, 1957, to the Upjohn Company; the patent outlined preparation via alkylation of d-desoxyephedrine with benzyl chloride and included early assessments of the compound's activity.^[29]

Regulatory approval

Benzphetamine hydrochloride, marketed under the brand name Didrex, received original approval from the U.S. Food and Drug Administration (FDA) on October 26, 1960, through New Drug Application (NDA) 12-427 held by Pharmacia & Upjohn Company. The approval was for 25 mg and 50 mg tablets indicated as a short-term adjunct in the management of exogenous obesity, for patients with an initial body mass index (BMI) ≥ 30 kg/m² who have not responded to appropriate weight-reducing regimens (diet and/or exercise) alone, as an adjunct to caloric restriction.^[35] In 1973, as part of the FDA's Drug Efficacy Study Implementation (DESI) program, the agency reviewed and confirmed the effectiveness of benzphetamine hydrochloride 25 mg tablets for the labeled indication, solidifying its regulatory standing post the 1962 Kefauver-Harris Amendments.^[36] Under the Controlled Substances Act of 1970, benzphetamine was classified as a Schedule III controlled substance effective May 1, 1973, reflecting its moderate potential for abuse relative to Schedule II substances but higher than Schedule IV. The prescribing information includes warnings regarding the risk of primary pulmonary hypertension and valvular heart disease, drawing from associations observed with serotonergic appetite suppressants like fenfluramine and dexfenfluramine in the 1990s; however, no such cases have been reported with benzphetamine monotherapy.^[35] Baseline cardiac evaluation, including echocardiography in patients with heart murmurs, is recommended prior to initiation, with discontinuation advised if new cardiac symptoms arise.^[35] Internationally, benzphetamine has seen limited adoption due to concerns over abuse potential and cardiovascular risks. In the European Union, it is listed in Schedule IV of the United Nations 1971 Convention on Psychotropic Substances and considered an obsolete pharmaceutical product in several member states.^[37] As of 2025, it remains available in the United States with restricted short-term prescribing but faces ongoing scrutiny amid evolving obesity pharmacotherapy options.^[5]

Society and culture

Brand names

Benzphetamine was formerly marketed under the brand name Didrex in the United States, developed and originally distributed by Pharmacia & Upjohn (now part of Pfizer), and available in tablet formulations of 25 mg and 50 mg. The Didrex brand has since been discontinued, with the drug now available only in generic form.^[3]^[1]^[2] Other brand names in the US include Regimex and Recede, though Regimex has been discontinued.^[38] Internationally, benzphetamine has limited availability and is typically sold under its generic name, benzphetamine hydrochloride, or the International Nonproprietary Name (INN) benzfetaminum in select regions, with no major trade name variations reported outside North America.^[1] Generic versions of benzphetamine became available following the expiration of patents on the original Didrex formulation in the 1970s, allowing multiple manufacturers to produce it as benzphetamine hydrochloride tablets.^[39] As of 2025, generic producers include Avet Lifesciences, Chartwell, Epic Pharma LLC, Impax Laboratories, and KVK-Tech Inc.^[39]^[1]

Legal status

In the United States, benzphetamine is classified as a Schedule III controlled substance under the Controlled Substances Act administered by the Drug Enforcement Administration (DEA), a designation effective since June 15, 1973.^[40] This schedule reflects its moderate potential for physical and psychological dependence, lower than that of Schedule I and II substances but higher than Schedule IV and V, attributable in part to its hepatic metabolism into active metabolites including amphetamine and methamphetamine.^[1] As a Schedule III drug, benzphetamine requires a prescription from a licensed healthcare provider and cannot be refilled without authorization; federal regulations allow up to five refills within six months, but clinical practice for appetite suppressants like benzphetamine typically mandates periodic re-evaluation to assess ongoing need and safety. It is not available over-the-counter anywhere in the world.^[15] Benzphetamine's abuse is regulated through state-based Prescription Drug Monitoring Programs (PDMPs), which track dispensing of Schedule III-V controlled substances to detect patterns of misuse or diversion. It holds the distinction of being one of the few amphetamine analogs classified as Schedule III, unlike most structurally related compounds placed in Schedule II due to higher abuse liability.^[41] Misuse or unauthorized distribution under the Controlled Substances Act carries penalties including fines up to $250,000 and imprisonment ranging from up to one year for simple possession (first offense) to up to five years for trafficking. Internationally, benzphetamine is listed in Schedule IV of the United Nations 1971 [Convention on Psychotropic Substances](/page/Convention_on_Psychotropic Substances), subjecting it to controls on manufacture, trade, and distribution while permitting medical and scientific use under strict oversight.^[42] In Canada, it is controlled as a Schedule I substance under the Controlled Drugs and Substances Act, prohibiting possession, trafficking, or production except for authorized medical purposes.^[43] The United Kingdom classifies it as a Class C drug under the Misuse of Drugs Act 1971, with penalties for unauthorized possession up to 2 years imprisonment and/or unlimited fines, and up to 14 years for supply or possession with intent to supply.^[44] In Australia, it falls under Schedule 4 (prescription-only medicines) of the Poisons Standard, requiring authorization for import, supply, and possession.^[45] It is prohibited in Japan under stimulant drug laws and similarly banned for non-medical use in Sweden as part of broader amphetamine restrictions. As of 2025, telehealth prescribing of benzphetamine remains restricted following the expiration of broad COVID-19 flexibilities under the Ryan Haight Online Pharmacy Consumer Protection Act; while a temporary extension allows it until December 31, 2025, providers must conduct an in-person evaluation for new patients or meet specific exceptions to avoid violations.

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[39]
[PDF] Scheduling Actions – Alphabetical Order
Oct 15, 2025 · 3/18/1994. I. AMOBARBITAL. 05-31-73. 11-13-73. 38 FR 31310. 11/13/1973. III --> II. AMPHETAMINE. 05-26-71. 07-07-71. 36 FR 12734. 7/7/1971. III ...
[40]
[PDF] Controlled Substances - Alphabetical Order
... Schedule, "CSCN" = Controlled Substance Code Number. Controlled Substances ... Benzphetamine. 1228. N. Didrex, Inapetyl. Benzylmorphine. 9052. Y.
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[PDF] List of Psychotropic Substances under International Control - INCB
Salts of all the substances covered by the four schedules, whenever the existence of such salts is possible, are also under international control.
[42]
Controlled Drugs and Substances Act ( SC 1996, c. 19)
Jun 4, 2025 · Federal laws of Canada. ... Benzphetamine (N-benzyl-N,α-dimethylbenzeneethanamine). (18). N-Propyl-3,4-methylenedioxy- amphetamine (α-methyl-N ...
[43]
Misuse of Drugs Act 1971, SCHEDULE 2 - Legislation.gov.uk
An Act to make new provision with respect to dangerous or otherwise harmful drugs and related matters, and for purposes connected therewith.
[44]
Schedule 4 Appendix D drugs - Prescribed restricted substances
Mar 21, 2023 · Benzphetamine; Bolandiol; Bolasterone; Boldenone; Bolmantalate; Bromazepam; Calusterone; Cathine; Chlorandrostenolone; Chlordiazepoxide ...