Adrafinil and Weight Loss | A-Z Guide

Nootropics researchers will note that while adrafinil has proven efficacy as a vigilance promoter, or cognitive enhancer, there is very little evidence of any connection between adrafinil and weight loss.

This guide seeks to outline all available research on the topic of adrafinil and weight loss. Besides summarizing adrafinil’s benefits, side effects, and potential effectiveness as a weight loss agent, this guide will also offer researchers a detailed overview of how this compound has been administered in past clinical trials and how it may be dosed in experiments moving forward.

Let’s dive in.

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What Is Adrafinil?

Adrafinil is a wakefulness-promoting substance that was first synthesized in France by scientists working for the Lafon Group in the 1970s [1]. Early animal studies found that it had a significant effect on nocturnal activity [2] and scientists pushed ahead with human clinical trials. In 1984, adrafinil was approved and released as a prescription wakefulness medication called “Olmifon,” and was primarily used to increase alertness in elderly patients [1].

Researchers studying adrafinil noticed that it was metabolized into two substances in the human body: CRL 4046 and modafinil [3]. Upon further study, modafinil was identified as the main active metabolite and was identified as likely responsible for most of adrafinil’s effects [4]. In 1994, the Lafon Group released modafinil in France under the proprietary name “Modiodal” and it subsequently gained widespread approval worldwide. Modafinil was approved by the United States Food and Drug Administration (“USFDA”) as a narcolepsy treatment in 1998 (under the name “Provigil”) and quickly became Lafon’s flagship product.

During the late 1990s and early 2000s, Olmifon fell into clinical disuse. It continued to be manufactured by Cephalon France, which acquired Lafon in 2002 [5], but production ceased in 2011 following a decision by the French medical authorities to revoke Olmifon’s marketing permission.

At the time of writing, adrafinil is available exclusively to researchers as a reference material or research chemical.

What does adrafinil do?

Adrafinil is a central nervous system (CNS) stimulant known as a eugeroic. It increases alertness and promotes vigilance [1]. Most of our understanding of adrafinil is based on clinical trials conducted in France and published in the French during the 1970s and 1980s. These trials involved elderly patients suffering from age-related difficulties with alertness. Data from these trials shows that adrafinil can produce the following effects [6, 7, 8, 9, cited in 10, 11, cited in 12]:

• Improved memory
• Better capacity to learn
• Enhanced alertness}
• Reduced fatigue
• Improvements on scores on intelligence measures
• Reduced confusion
• Improved reaction time
• Improved mood

How does adrafinil work?

Adrafinil’s exact mechanism of effect is not yet known; however, most scientists believe that modafinil is responsible for much of its effects [1]. Modafinil has been much more widely studied than adrafinil, having been shown to produce the following effects:

1. Blocking dopamine reuptake: Modafinil is a weak dopamine reuptake inhibitor that causes levels of dopamine to rise [13]. Dopamine is likely responsible for the improvement in mood reported by patients who are administered adrafinil and modafinil.
2. Blocking norepinephrine reuptake. Norepinephrine plays a role in preparing the body for movement and action [14]. By blocking norepinephrine’s reuptake, more of it stays in the nerve synapse and so it has a prolonged effect.
3. Influencing neurochemicals: Modafinil plays a role in regulating orexin, serotonin, GABA, and histamine [15], all of which play a role in regulating wakefulness and sleep cycles.
4. Increasing brain metabolism. Modafinil, and adrafinil by extension, both increase the rate at which the brain functions and burns fuel [1].

It is prudent to again note that even though the research on adrafinil began in the 1970s, it remains largely under-researched compared with modafinil. Researchers should bear this in mind as we review potential links between adrafinil and weight loss.

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Adrafinil Side Effects and Safety

What little we do know about adrafinil’s side effects and safety comes from clinical trials involving elderly patients [6, 7]. It is no longer available as a prescription drug (Olmifon was discontinued in 2011) and has effectively been replaced by modafinil (Modiodal/Provigil) in clinical practice (i.e. in the treatment of sleepiness associated with narcolepsy and other sleep disorders). Researchers interested in exploring adrafinil’s side effects should be careful to avoid extrapolating historical trial data to theorize on how this compound may affect non-elderly populations.

Nevertheless, an Olmifon product summary produced by Cephalon France provides a useful summary of all side effects and safety issues observed during human trials. This document states that adrafinil may cause the following side effects when dosed at 600-1,200 mg/d [16]:

• Headaches
• Mood swings
• Agitation
• Rashes
• Insomnia
• Confusion and/or aggression
• Gastralgia
• Tremors
• There are several known cases of adrafinil causing oral-facial dyskinesias [17].

According to the Olmifon product summary, adrafinil must not be administered to subjects who are pregnant and must be used at a lower dose (300-600 mg/d) by subjects with chronic hepatic and/or renal impairment.

To date, adrafinil has not been linked to any cases of overdose deaths (accidental or otherwise).

Having reviewed the documented side effects and safety issues associated with adrafinil, the following section will review the literature regarding adrafinil and weight loss.

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Adrafinil and Weight Loss | What You MUST Know

Researchers curious about adrafinil and weight loss will find an overview of all available research in this section.

Weight-loss basics

For purposes of this guide, the terms “weight loss” and “fat loss” will be used interchangeably. Many factors determine how efficiently a test subject’s body can burn fat, including their diet, activity levels, genetics, and gut health. Below, we will focus on research involving adrafinil and its active metabolite modafinil, and will not consider any of subject-specific factors in detail. A subject’s ability to achieve fat loss from adrafinil administration will vary.

Does any research connect adrafinil with weight loss?

The short answer is “no.” To date, there are no clinical studies involving adrafinil that show any connection between adrafinil and weight loss. We have not found any published studies on animal models or humans that have addressed the effects of adrafinil on weight loss [1]. However, animal studies have shown that adrafinil produces an increase in locomotion accompanied by a decrease in sleep which could, in theory, create the right conditions for fat loss to occur.

Evidence suggests modafinil could contribute to weight loss

Despite the lack of trial data showing any connection between adrafinil and weight loss, there have been some studies on modafinil and weight loss under highly specific clinical conditions. While modafinil is not the same as adrafinil, it is believed to be responsible for most of the latter compound’s effects. Accordingly, these studies may help inform the direction of future research into adrafinil and weight loss.

A 2004 study by Makris et al. found that modafinil affected appetite in healthy adults aged 21-35 [18]. Researchers found that modafinil significantly decreased the total calories consumed, in effect creating the type of conditions where weight loss may occur.

A 2008 study by Perez et al. found that shift workers given both 200 mg and 400 mg doses of modafinil significantly reduced their total caloric intake and had lower perceptions of hunger [19]. The study’s authors actually suggested that modafinil could be further tested as a treatment for obesity.

Some other studies have found that modafinil may be useful in avoiding weight gain that typically occurs with other medications. For example:

• Modafinil administered together with clozapine, an antipsychotic medication, resulted in significant weight loss [20].
• Modafinil helped participants taking the antipsychotic medication olanzapine avoid gaining as much weight as a placebo group [21].
• Modafinil seemed to reduce the appetite increase and the weight gain that is common among patients with atypical depression [22].

While none of these trials involved adrafinil, the findings indicate, though do not prove, that adrafinil, as a prodrug of modafinil, may produce similar effects when administered to test subjects in comparable doses.

Some research did not find an effect of modafinil on weight loss

Researchers interested in adrafinil’s potential as a weight-loss compound should also consider research where no link between modafinil and weight loss was established.

For example, a 2008 study by Sudhakar et al. found that even though modafinil led to significant weight loss in patients taking antipsychotic medications compared to their baseline weight, there was no difference between changes in their weight compared with a placebo control group [23].

A separate study by Schinkelshoek et al. found that in the case of narcolepsy patients being administered modafinil, the subjects experienced an increase in their body mass index (BMI) readings [24].

Further research is needed to clarify the effect of modafinil on body weight and fat loss.

How could adrafinil “work” for weight loss?

As previously stated, there is no direct evidence linking adrafinil with weight loss, while the evidence linking modafinil to weight loss remains inconclusive. Our understanding that adrafinil can increase activity and therefore stimulate weight loss is based largely on findings from animal studies [9 cited in 10, and 11 cited in 12]. But the notion that increased activity is a proven behavioral response to adrafinil is far from certain. Edgar and Seidel [22 cited in 1] concluded that an increase in the activity of mice following adrafinil treatment was likely due to the reduced time they spent asleep.

This supports the conclusion that adrafinil is not a weight loss pill and any effects of adrafinil on weight loss would come through modulation of appetite and of neurotransmitters, helping the subject eat less and exercise more.

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Is Adrafinil Weight Loss a Good Idea?

Speculating about whether researchers should administer adrafinil to test subjects to test its effects on weight loss is beyond the scope of this guide, but the available literature shows no indication that adrafinil has any effect on weight loss.

At best, we might speculate that adrafinil—through its active metabolite modafinil—may produce similar effects to those observed following the administration of modafinil to test subjects in past clinical studies [18, 19, 20, 21, 22].

How to take adrafinil for weight loss

Researchers interested in exploring adrafinil’s efficacy for weight loss may consider past clinical trials involving both adrafinil and modafinil to calculate the optimum dose and duration of the experiment.

Past adrafinil studies have typically dosed this compound at 900 mg/d for up to 90 days [6, 7], while elderly patients prescribed Olmifon to increase vigilance have taken doses in the range of 600-1,200 mg/d [16]. Guidance from Cephalon France stated that patients should take adrafinil first thing in the morning on an empty stomach to minimize absorption time [16].

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Losing Weight with Adrafinil | Verdict

At the time of writing, adrafinil is a research chemical that has not shown efficacy as a weight-loss compound. Our review of the available literature shows that modafinil, which is adrafinil’s main metabolite, may be effective in reducing appetite and stimulating weight loss, but findings remain inconclusive. This strongly suggests that further research into adrafinil’s effect on weight loss is warranted and may prove fruitful.

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