Deanol for ADHD

A few decades ago, Deanol was used as an ADHD medication.¹² A daily dose of 300 mg in the morning was recommended for the first three weeks (= until the onset of action) and then a maintenance dose of 100 to 300 mg daily.³

We do not consider the following results to be particularly impressive, but they cannot be completely dismissed, especially with regard to hyperactivity.
In our opinion, despite its relatively low Effect size (compared to AMP and MPH), Deanol could, due to its low risk of side effects (although this is likely to be relativized at higher and thus more effective doses) at least

• if MPH, AMP, ATX and guanfacine are ineffective
• in case of intolerance to MPH, AMP, ATX and guanfacine (e.g. loss of appetite)
• for weaker cases

be worth a second look.

Since medical clearance is mandatory before the first intake due to the considerable risk of contraindications and side effects in some cases (self-medication experiments are dangerous!), a longer waiting time for the adjustment to MPH or AMP should barely be considered a serious reason. This applies all the more in view of the long time it takes for the drug to take effect (3 weeks). In practice, bridging the use of Deanol until dosing with MPH or AMP is only possible if accompanied by a GP, while waiting for dosing by a psychiatric specialist. This GP would have to be very committed, as deanol has completely disappeared from current prescribing practice and no doctor is likely to have any experience of it. The following collection of many relevant studies and findings on deanol could help here.

After all, Deanol is not classified as a BtM and is freely available as a dietary supplement. One study reports that it does not inhibit appetite, which would be a major advantage over other stimulants. However, the risks and contraindications should be carefully considered. It is also completely unclear how long the effect of a single dose of Deanol lasts. The fact that the onset of action can take 3 weeks opens up the cautious hope of an all-day effect, as is the case with other drugs with such a long latency to onset of action. On the other hand, the long latency of action massively increases the difficulty of dosing.

• 1. Preparations
• 2. Synonyms
• 3. Pathways of action of Deanol
• 4. Deanol for ADHD
• 5. Deanol for other disorders
• 6. Interactions, contraindications and side effects
  • 6.1. Interactions of Deanol
  • 6.2. Contraindication of Deanol
  • 6.3. Side effects of Deanol

1. Preparations¶

Monopreparations: Germany: Risatarun. Russia: Nooclerin. US. Deaner.
Deaner (deanol p-acetamidobenzoate) from Riker Laboratories was a prescription drug in the USA for 20 years and was withdrawn from the market in 1983.⁴ Risatarun is also no longer available.
According to a study conducted in an American clinic between 1956 and 1960, deanol was the most frequently prescribed first drug (ahead of chloropromazine, diamine (captodiamine), meprobamate and imipramine).⁵ Deanol was used for a wide range of disorders⁶

Deanol is still freely available as a dietary supplement. The maximum recommended daily dose for adults is 240 mg.
Combination preparations with deanol are also available (Switzerland: Pharmaton Vital Geriavit; Germany: Vita Gerin; the package leaflet does not state this, however, but refers to choline tartrate). However, at 40 mg, these contain significantly less than the daily doses of deanol previously tested for ADHD. Due to the other ingredients, we strongly advise against taking several doses of the combination preparations.

2. Synonyms¶

3. Pathways of action of Deanol¶

Deanol acts as a stimulant when administered chronically.¹⁴¹⁵¹⁶ While amphetamine has an immediate stimulating effect, this effect is delayed with deanol and appears to occur via pathways that are subject to saturation¹⁷

Deanol crosses the blood-brain barrier. However, only small amounts enter the brain in the first 5 minutes, while a higher level is reached in the brain over 24 hours⁶

How deanol relates to choline and acetylcholine is still unclear.
Deanol is a close structural analog of choline, an essential nutrient, but¹⁸ does not completely replace it.¹⁹

Three possibilities are described for the mode of action of Deanol:²⁰

• Deanol could be a precursor of choline and thus of acetylcholine^{1521 15 22} whereby the acetylcholine could then be responsible for a stimulating effect.

  • This is contradicted by
    • That deanol did not increase the total acetylcholine content in the rat brain²³²⁴
    • That deanol could not prevent damage from a low-choline diet in a choline-dependent mouse model¹⁹
      • However, others report increased choline levels and only with very high danol administration also increased acetylcholine levels in the brains of the damaged rat pups²⁵²⁶
      • However, since deanol inhibits the transport of choline through the blood-brain barrier, this is not a compelling argument against deanol as a precursor of choline
  • Deanol increased the choline content in the CNS, but was only half as effective as centrophenoxine (meclofenox), which dramatically increased the choline level in the CNS of rats. In the hippocampus, this increase in choline content was accompanied by a new, increased acetylcholine (ACh) level. No such coupling was observed in the striatum or parietal cortex. The changes in choline levels were probably mainly extracellular. Despite the changes in choline and ACh levels, no consistent changes in ACh turnover were measured.²⁷
  • Deanol increases the choline level in the blood²⁸
    • However, an increase in choline levels in the brain could fail because deanol competes with choline transport at the blood-brain barrier²⁹
    • A study showing that administration of deanol increased acetylcholine levels in the striatum of rats suggests that acetylcholine levels may be limited by the amount of the precursor deanol³⁰
    • Deanol inhibits the uptake of choline into the brain, as it binds five to 10 times more strongly to the transporters of the blood-brain barrier than choline.^31323334 However, the choline-blood-brain barrier inhibition by deanol is much weaker than by hemicholinium-3.³⁵
  • Deanol i.V. or orally increased choline, but not acetylcholine in the brain of rats²⁸
  • Deanol increased choline in kidney and liver³⁶
  • A recent study found no evidence that deanol alters the absorption and distribution of choline, or that deanol is converted to choline in vivo.¹⁸
  • A low-choline diet did not reduce acetylcholine levels³⁷
  • Deanol increased acetylcholine levels in the brain of rodents only in the striatum and only at high doses (900 mg / kg injected into the abdomen)²⁶

• Deanol could act at the cholinoceptive receptor sites due to its structural similarity to acetylcholine

  • This is contradicted by the fact that atropine does not block the central vasomotor stimulating effect of deanol, while the effect of acetylcholine and carbachol is blocked by atropine
  • However, another study reported that atropine temporarily weakened the effect of deanol³⁸

• Deanol could act on receptors other than cholinoceptive receptors to produce its stimulatory effect, and instead have a direct stimulatory effect on the vasomotor center

• Deanol acted on cerebral cortex neurons like acetylcholine³⁹

• Deanol is a radical scavenger.¹⁰

• Deanol alleviates the exploratory hyperactivity resulting from intermittent postnatal hypoxia in the rat (2nd-10th day of life after birth), while piracetam even eliminates it. The deanol was administered to the mothers (from the 12th day of gestation) and to the newborns (from birth to the 10th postnatal day of life). The perinatal administration of deanol (unlike piracetam) reduces the consequences of postnatal oxygen deficiency in terms of motor activity and dopamine release in adult animals.⁴⁰

4. Deanol for ADHD¶

Studies on the effect of deanol in children with ADHD reported:

• similar effect to stimulants¹⁵
• Hyperactivity reduced⁶¹⁶²⁶³
  • Deanol reduces the hyperactivity tripled by inorganic lead in mice for a good one and a half hours, temporarily to normal values.⁶⁴ In controls not exposed to lead, the same dose of deanol led to an equally long-lasting observable behavioral arousal and stimulation of motor activity.
• Learning ability increased⁶¹⁶²
• Reduced irritability⁶¹⁶²
• Behavioral problems especially in hyperkinetic children with moderate unhappiness and isolation⁶⁵
• Improvement in the functional capacity of children with behavioral problems (at 100 mg/day)⁶³
• Increased attention span⁶³
• Executive functions (organization) improved⁶³
• Improved performance when solving puzzles and problems
• Improved motivation for learning tasks, resulting in increased learning success for rats in the water maze⁶⁶
• “spectacular” results in 22 of 27 hyperkinetic children at doses up to 400 mg / day⁶⁷
• Improvements in 25 of 33 children with behavioral problems (78%), deterioration in 7 of 33 (21%), with these 7 children showing a cerebral rhythm disturbance on the EEG⁶⁸
• Improvement in 2 case studies with ADHD⁶⁹
• no improvement compared to placebo at 100 mg deanol⁷⁰
• 10 to 30 mg showed no significant changes in blood pressure, pulse rate, muscle strength, hand tremor, vital capacity, body weight or blood cholesterol levels in healthy volunteers. There were significant psychological and subjective reactions: increased muscle tone, better mental concentration, less need for sleep, calmer sleep and absence of the usual morning fatigue phase⁷¹

A review revealed:⁷²

• the better controlled studies generally found little or no effect on ADHD
• the most promising use is for behavioral problems, particularly hyperkinetic impulse disorder and cases of poor classroom behavior and impaired attention, at doses in the range of 150 to 300 mg for children aged 6-12 years and administered for at least 3 months

A meta-analysis compared Deanol with various other ADHD medications:⁷³

Active ingredient	Positive effect	Negative effect	Side effects	n (test subjects)
Methylphenidate	83 %	1 %	14 %	n = 337
Amphetamine (Dexedrine, Benzedrine)	69 %	11 %	12 %	n = 610
Chlordiazepoxide	60 %	17 %	18 %	n = 237
Chlorpromazine	55 %	4 %	25 %	n = 123
Deanol 50 - 150 mg	47 %	9 %	7 %	n = 239
Reserpine	34 %	0 %	1 %	n = 165

A placebo-controlled study of 41 to 45 children aged 6 to 12 years with ADHD found improvements with 300 to 500 mg deanol over 3 months that were statistically significant or very slightly below the significance threshold (p = 0.05 to 0.07).⁷⁴

5. Deanol for other disorders¶

Other potential fields of application for Deanol:

• ASA: 1.8 reported improvements per reported worsening (n = 121)⁷⁵ High-dose B6 and magnesium achieved 8.5 reported improvements per reported worsening (n = 318) Fenfluramine (n = 104):1.5:1. Thioridazine hydrochloride (Mellaril) (n = 724): 1.4:1.
• Depression:
  • A study reports very good results⁷⁶
  • Deanol inhibits the depressive effect of barbiturates⁴
  • One study found a non-significantly better effect of 40 mg deanol on mild depression⁷⁷
• Alcohol withdrawal: reduced withdrawal symptoms, no side effects⁷⁸
• Tension headache (preventive use). Deanol significantly reduced the frequency, duration and intensity of tension headaches, a regression of fatigue symptoms and a normalization of the sleep-wake rhythm.⁷⁵⁷⁹
• asthenic and cognitive disorders⁸⁰
• Enuresis (improvement in 11 of 19 children with behavioral problems, 58%)⁶⁸
• Autonomic dysfunction / dysautonomy⁸¹
• Neurasthenia in adolescents with school difficulties aged 14 to 17 years. Symptoms included autonomic disorders, decreased attention and reaction time and increased reactive anxiety, significantly decreased alpha rhythm spectrum in the occipital leads in qEEG. Deanol improved symptoms in 68.8% of subjects, but not anxiety symptoms.⁸²
• protective effect against streptozotocin-induced diabetes mellitus and stress-induced erosive ulcer damage of the gastric mucosa when administered perorally at a dose of 250 mg/kg per 24 hours over 4 days. The effect was supported by an activation of intestinal peristalsis and an increase in blood flow in the gastric wall.⁸³
• Deanol is said to promote lucid (conscious) dreams⁸⁴
• Positive effect on visual function and the antioxidant activity of tear fluid in patients with primary open-angle glaucoma⁸⁵
• anaphylactoid edema produced in the paws of rats by subplantar injection of protein, serotonin, formaldehyde or histamine were ameliorated by deanol acutely by intraperitoneal injection and, with a time delay, also by chronic oral administration. The presence of the adrenal glands was not required. Deanol was ineffective in inflammatory reactions of the cotton pellet granuloma type.⁸⁶
• Skin-tightening effect with external application⁸⁷⁸⁸

Deanol proved to be ineffective to ineffective in:

• Tardive dyskinesia⁸⁹ Tardive dyskinesia or tardive dyskinesia is a movement disorder triggered by prolonged use of dopamine antagonists (neuroleptics/antipsychotics) and persisting after their discontinuation.
• Schizophrenia (no better than placebo)⁹⁰
• Alzheimer’s disease⁹¹
• Amnestic disorders⁹²
  • however, an inverted-U curve of the optimal dosage of deanol in relation to memory impairment is reported³²

6. Interactions, contraindications and side effects¶

6.1. Interactions of Deanol¶

Deanol (175 to 350 mg/kg, subcutaneous) increased the effect in the CNS of rats⁴

• Cardiazole
• Strychnine
• Morphine
• Chlorpromazine
• Evipan
• Phenobarbital

Deanol can⁹³

• weaken anticholinergic medication.
• interact with acetylcholinesterase (AChE) inhibitors (as used in the treatment of Alzheimer’s disease)
• interact with colinergic drugs (such as those used to treat glaucoma, Alzheimer’s disease and other diseases)

Deanol in combination with a low choline diet can have significant side effects⁹⁴, as deanol inhibits the transport of choline through the blood-brain barrier.³²

6.2. Contraindication of Deanol¶

• Deanol is contraindicated in epilepsy/convulsive disorder or bipolar Disorder. At 20 mg/day (0.084 mmol), there was a gradual increase in muscle tone and possibly an increased frequency of convulsions in susceptible individuals⁴
• Schizophrenia⁹⁵⁴
• Deanol must not be taken during pregnancy and breastfeeding.⁴ Inhibition of choline uptake and choline metabolism during neurulation caused growth retardation and developmental disorders of the neural tube and face.⁹⁶

We suspect that deanol may be contraindicated in homocystinuria (excessive homocysteine levels). Deanol is an inhibitor of betaine synthesis in the kidney.⁴³ Betaine is helpful in homocystinuria.⁹⁷ At the very least, a possible influence on the betaine dosage should be discussed with the doctor.

6.3. Side effects of Deanol¶

Most studies speak of minor side effects, even with prolonged use.⁶⁸
In humans, deanol has no effect on blood pressure, pulse rate or appetite. The side effects are minor and include headaches, constipation, insomnia, skin rash and muscle tension.³

At high doses, one study reported that 5 of 38 patients showed depressive and 3 hypomanic reactions. 7 of these 8 persons with ADHD had previously shown affective disorders.²⁹
In a successful treatment of an essential tremor existing since early adulthood over 10 years, a pronounced developing dyskinesia syndrome, which mainly affected the orofacial and respiratory muscles, was reported (individual case report).⁹⁸

An injection (not typical for medication) directly into the cerebrospinal fluid of dogs led to a slight increase in blood pressure over about 3 hours.²⁰