A rare case modafinil dependence

Krishnan, Raman; Chary, Krishnan Vengadaragava

doi:10.4103/0976-500x.149149

Cited by 53 publications

(26 citation statements)

References 6 publications

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“…In either case, the reductions in ICSS thresholds produced by the higher dose of MOD was less robust (≤ ~10%) than those produced by the higher doses of cocaine (~10–20%). Taken together, these findings indicate that only supraphysiological doses of MOD facilitate brain reward function, which is consistent with recent reports of abuse and dependence in humans produced by high doses of the drug [3, 12, 14, 15, 32]. In addition, the lack of robust effects of MOD on ICSS thresholds is also consistent with animal studies that have failed to demonstrate rewarding or reinforcing effects of this drug in place preference and self-administration paradigms [7, 11, 26].…”

Section: Discussionsupporting

confidence: 91%

“…While their precise therapeutic mechanisms of action are not fully understood, several lines of research indicate that at therapeutically relevant doses, MOD and R-MOD inhibit the reuptake of dopamine via presynaptic dopamine transporters (DAT), and exhibit DAT occupancy similar to that of methylphenidate [17, 18, 21, 37]. While post-FDA approval surveillance studies have not revealed significant patterns of MOD or R-MOD abuse, a small collection of both preclinical and clinical studies suggest that these drugs, particularly at high doses, may possess a degree of abuse liability that is higher than previously thought [3, 12, 14, 15, 32, 36]. …”

Section: Introductionmentioning

confidence: 99%

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Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence

2015

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Background Modafinil and its enantiomer R-modafinil are approved for the treatment of various sleep disorders, and may also be efficacious in the treatment of psychostimulant abuse. However, the ability of modafinil and R-modafinil to alter brain reward function has not yet been assessed. Purpose This study assessed the effects of modafinil and R-modafinil on brain reward function using the intracranial self-stimulation (ICSS) paradigm. Study design Male Sprague-Dawley rats were trained to respond for ICSS using current-intensity threshold determination procedures. Changes in ICSS thresholds were then assessed following administration of modafinil and R-modafinil (50, 100, and 150 mg/kg), or cocaine (2.5 – 20 mg/kg) as a positive control. Results ICSS thresholds were reduced by modafinil at the 150 mg/kg dose, as well as by cocaine at the 10 and 20 mg/kg doses. R-modafinil only produced non-significant trends towards reducing ICSS thresholds. Conclusion Modafinil and R-modafinil have limited effects on brain reward function in otherwise drug-naïve subjects. Additional assessments of these effects in the context of psychostimulant dependence are needed.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence

2015

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“…It has been demonstrated that, similar to cocaine in humans, modafinil increases dopamine release in the nucleus accumbens by blocking the dopamine transporter (DAT) (Volkow et al, 2009; Funayama et al, 2014) and can produce withdrawal symptoms once its use is discontinued (Krishnan and Chary, 2015). In a study using animal models, Bernardi et al (2009) have demonstrated that modafinil at high doses reinstated cocaine-induced conditioned place preference following extinction in rats.…”

Section: Introductionmentioning

confidence: 99%

Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

et al. 2016

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There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

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“…In literature, we could find only two case reports on modafinil dependence at higher doses 2,5). As seen in the index case, modafinil seems to have some abuse potential.…”

Section: Discussionmentioning

confidence: 90%

“…Overdose of modafinil can cause insomnia, agitation, tachycardia, rise in blood pressure etc., but in case of dependence it is more likely to cause physical withdrawal symptoms like lethargy, tremors of hands, anxiety and erratic sleep hours5) or only severe psychological withdrawal symptoms 10). Modafinil has been listed under schedule IV drug in United States for regulation of its sale.…”

Section: Discussionmentioning

confidence: 99%

Modafinil Dependence and Hypersexuality: A Case Report and Review of the Evidence

Sahoo

Subodh

Gupta

2016

Clin Psychopharmacol Neurosci

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Apart from sleep wake disorders, nowadays, modafinil is being prescribed for several psychiatric disorders including depression. Despite being reported as to be having very low abuse potential, cases of modafinil dependence had come to the limelight. In this case report, we describe a 35 year old man with bipolar affective disorder while in remission who developed modafinil dependence and later on, had hypersexuality when he increased the dose of modafinil from 400 to 1,000 mg/day. Existing literature suggests that modafinil when taken above prescribed doses can cause many side effects ranging from nausea, vomiting to psychotic exacerbation and mania. However, hypersexuality as a side effect of modafinil overuse is not commonly seen. The exact pathophysiological mechanism of modafinil induced hypersexuality is not clear. Clinicians should be aware of possibility of modafinil leading to dependence and this rare significant side effect of modafinil.

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A rare case modafinil dependence

Cited by 53 publications

References 6 publications

Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence

Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence

Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

Modafinil Dependence and Hypersexuality: A Case Report and Review of the Evidence

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