Substance abuse with self-medication effect in ADHD

On closer inspection, some misuse of addictive substances appears to be self-medication. This does not change the fact that they are abused or even punishable by law. In addition, the desired effect of normalization is not achieved and considerable unpleasant side effects occur. However, the tendency to prefer certain drugs can provide information about the causes of substance abuse.

ADHD is characterized, among other things, by an increased number of DAT. One study reports a significant reduction in DAT in ADHD sufferers who were also users of dopaminergic drugs.¹

• 1. Nicotine
• 2. Cannabis: THC, cannabidiol
  • 2.1. Cannabinoids (THC)
    • 2.1.1. Cannabinoids influence dopamine, serotonin and acetylcholine in the PFC
    • 2.1.2. Increase in the cortisol level
    • 2.1.3. HPA axis shutdown due to THC-mediated cortisol increase?
    • 2.1.4. Reduced cortisol response to acute stressors
    • 2.1.5. Reduction of the amygdala volume
    • 2.1.6. Cannabinoids change the EEG: alpha increases, beta decreases
    • 2.1.7. Cannabis abuse correlates with ADHD symptoms, not cognitive problems
  • 2.2. Cannabidiol (CBD)
  • 2.3. THC medication for ADHD
  • 2.4. ADHD symptom improvement through microdosing
• 3. Amphetamines / Mesamphetamines
• 4. Cocaine
• 5. Alcohol
• 6. LSD

1. Nicotine¶

Nicotine and methylphenidates are both stimulants. They have similar effects.² Both nicotine and methylphenidate reduce the number of dopamine transporters (DAT)³ in the medium term and - also as a result - increase the availability of dopamine in the synaptic cleft.⁴
Empirical evidence shows that non-medicated ADHD-HI sufferers smoke significantly more often than medicated ADHD-HI sufferers or non-sufferers.⁵

The increased risk of ADHD due to maternal smoking during pregnancy (more on this at ⇒ Nicotine consumption of the mother during pregnancy In the article ⇒ Environmental factors as a cause of ADHD in the chapter ⇒ Emergence) is probably at least partly due to the increased likelihood of passing on the genetic disposition that made the mother herself an ADHD sufferer. In addition, the fact that a woman cannot stop smoking despite being pregnant indicates firstly that nicotine is very much needed, secondly a lack of self-control and thirdly a lack of care for the child entrusted to her care. Also with regard to the fact that this occurs more frequently in lower socio-economic classes than in more affluent classes, the question arises as to whether belonging to a social class is the result of impaired self-regulation or vice versa. In any case, low socioeconomic status correlates with an increased risk of ADHD.

• Nicotine significantly increases adrenaline levels and tends to reduce noradrenaline levels. Nicotine therefore improves test results and reaction times.⁶⁷⁸
• Nicotine patches have shown a positive effect on ADHD in a double-blind study.⁹¹⁰¹¹
• Nicotine or smoking is said to considerably increase the risk of depression and significantly worsen mood.¹² Psylex also cites a study that showed a clear causality of smoking for depression, but not of depression for smoking. Unfortunately, this source could not be verified.
• Smoking significantly reduces the number of dopamine transporters in the striatum. An increased number of dopamine transporters is said to be a typical phenomenon in ADHD. In a SPECT examination of 31 adults with ADHD, a greater increase in DAT was found in ADHD-HI sufferers than in ADHD-I sufferers. However, DAT were still elevated in ADHD-I sufferers compared to non-sufferers. Smoking significantly reduced DAT in both subtypes.¹³
• A study of smokers with ADHD found that those with mild ADHD showed reduced inhibition and increased impulsivity after taking a break from smoking, while this was surprisingly not the case for those with severe ADHD.¹⁴

2. Cannabis: THC, cannabidiol¶

Abuse of hashish/cannabis/marijuana is very common among ADHD sufferers.
A study found cannabis use in 14.3% of all ADHD sufferers, while only 4.3% of those not affected use cannabis. ADHD thus increases the likelihood of cannabis use more than threefold.¹⁵ Hyperactive individuals also started using cannabis much earlier than those who were purely inattentive.

The assumption that this is due to the relaxing to sedative effect is questionable due to the stimulating and energizing effect on biomarkers. Nevertheless, cannabis appears to effectively reduce “inner pressure”.

The active ingredients are primarily the psychoactive cannabinoids (such as THC = dronabinol) and the non-psychoactive cannabidiol (CBD).

2.1. Cannabinoids (THC)¶

2.1.1. Cannabinoids influence dopamine, serotonin and acetylcholine in the PFC¶

Cannabinoids influence dopamine, serotonin and acetylcholine in the PFC.¹⁶ Deficits in working memory, attention function and reversal learning with THC use as a drug appear to be mediated by activation of the CB1 cannabinoid receptor.
The positive effect of THC as a drug or in microdosing use (without intoxication) could possibly be mediated by this. More detailed information on this is lacking.

2.1.2. Increase in the cortisol level¶

One connection could be that THC (in non-THC addicts) increases cortisol levels in a dose-dependent manner.¹⁷¹⁸ This had previously been established in animal experiments.¹⁹ However, another study found no change in cortisol levels due to THC.²⁰
Cannabinoids generally influence the activation of neurotransmitters such as GABA and glutamate, which regulate the stress axis; THC activates the HPA axis.²¹ When the cortisol level was measured 4 hours after THC administration, it was not (no longer) elevated.²²
In drug users who had been abstinent for at least 2 weeks at the time of the study, no increase in cortisol to THC was detected.²³ This could possibly be the result of receptor downregulation.

2.1.3. HPA axis shutdown due to THC-mediated cortisol increase?¶

We consider it theoretically conceivable that a (rare and mild) THC high could possibly produce a relaxing effect in that the resulting increased cortisol release effectively shuts down the HPA axis in ADHD-HI and ADHD-C sufferers. ADHD-HI and ADHD-C sufferers (with hyperactivity) have a flattened cortisol response to stress, whereas ADHD-I sufferers show an exaggerated cortisol release from acute stress. As cortisol not only mediates stress symptoms, but (as the last stress hormone released by the HPA axis) also has the task of down-regulating the HPA axis, (at least some) ADHD-HI and ADHD-C sufferers lack the regular deactivation of the HPA axis by cortisol.
However, this presumably only applies to occasional users and not to long-term users of THC, in whom receptor downregulation may prevent this effect.
This hypothesis correlates with the fact that THC is primarily consumed by ADHD-HI sufferers. ADHD-I sufferers, who have no HPA axis shutdown problem due to their excessive cortisol response to stress, are less likely to consume THC.
This thesis further correlates with the reports of ADHD-HI sufferers that after THC use, the calmness gained from it lasts for about 2 to 3 days.

2.1.4. Reduced cortisol response to acute stressors¶

In long-term users who consume THC every day or almost every day (probably due to downregulation or upregulation ⇒ Downregulation / upregulation) the cortisol response to acute stressors is reduced.

In long-term users, THC can therefore no longer trigger downregulation of the HPA axis by cortisol due to the lack of an increase in cortisol release.
The reduced cortisol response to acute stress in long-term THC users²⁴²⁵ could explain the assumption of a high cortisol output by THC and a resulting special THC affinity of people with a flattened cortisol response to stress.

2.1.5. Reduction of the amygdala volume¶

There is evidence that prolonged cannabis use reduces the volume of the amygdala and hippocampus.²⁸
It is conceivable that reducing the size of the amygdala also reduces its activity and that such a reduction in amygdala activity reduces the intensity of stress reactions.
Unfortunately, this is not the only effect of cannabis.

The problem is that even infrequent use can lead to addiction, which is why therapy cannot be advocated even for infrequent cannabis use.
On the other hand, ADHD-HI sufferers (especially those with comorbid aggression disorders) report that continuous use also gives them an inner serenity that cannot be achieved in any other way.
Continuous users of cannabis with ADHD are characterized by increased hospital admissions and reduced use of medication and behavioural therapy.²⁹

2.1.6. Cannabinoids change the EEG: alpha increases, beta decreases¶

Cannabis increases activity in the alpha band of the brain and decreases activity in the beta band and the other frequencies of the EEG.³⁰³¹³²
The fact that cannabis increases alpha activity (which is necessary for concentration) beyond acute consumption while simultaneously reducing the activity of all other frequencies (including beta frequencies, which prevent adequate relaxation when increased, e.g. thought circles) could explain why cannabis is perceived as pleasant by many ADHD sufferers. It is understandable that this effect is not beneficial in terms of the overall constitution in the long term. It is also plausible that this effect has a short-term relieving effect for ADHD sufferers.

2.1.7. Cannabis abuse correlates with ADHD symptoms, not cognitive problems¶

A larger study found a correlation between cannabis abuse and ADHD symptoms such as hyperactivity/impulsivity and inattention. Whether cannabis abuse was the cause/trigger or consequence of the symptoms (self-medication) was not investigated. Furthermore, the study found no correlation between cannabis abuse and cognitive problems.³³

2.2. Cannabidiol (CBD)¶

Cannabidiol (CBD) is not psychoactive and is another relevant component of cannabis alongside cannabinoids (THC).

Cannabidiol reduces anxiety after a stress test, but not before or during.³⁴

A comparison of different doses showed that cannabidiol only reduced anxiety during and after a stress test at low doses (300 mg), but not at 600 mg or 900 mg.³⁵ Another study comparing the effect of 600 mg cannabidiol against placebo in social phobia sufferers found an anxiety-reducing effect during the stress test, although more anxiety was still reported than in non-affected individuals.³⁶

Anxiety sufferers told us that taking CBD hemp oil enabled them to significantly reduce their anxiolytic medication.
An effect of CBD on ADHD has not been reported.

2.3. THC medication for ADHD¶

THC drugs (which do not cause a high due to the dose, but are rather designed to have a constant long-term effect) can have a positive effect on ADHD symptoms.

• THC is a drug of choice for ADHD sufferers. The relaxing effect is appreciated, which some sufferers describe as lasting for 2 to 3 days after use. This long-lasting effect (in occasional users, not in continuous users) could possibly be the result of a down-regulation of the HPA axis by the cortisol release caused by THC.
• THC stimulates the reward/reinforcement center of the brain. This is precisely where one of the central neurological problems with ADHD lies: too little dopamine in the striatum.
• Whether THC actually increases the release of dopamine in the brain’s reward center, the striatum, is unclear. Some studies affirm this,³⁷³⁸ others deny it.³⁹ To summarize Pertwee.⁴⁰ Since dopaminergic intoxicants function by increasing dopamine levels in the brain’s reinforcement center, and intoxication is based on a massive short-term excess of dopamine, an increase in dopamine levels by THC would be plausible. Apart from the fact that consumption as a drug causes a rapid increase in dopamine above the functional level, whereas medication causes a slow increase to a constant (functional) level, the short-term effect also changes at the latest with long-term use: in THC addicts, the dopamine level in the striatum is reduced.⁴¹ This raises the question of whether this is a consequence of dependence (which would be logical, as a permanently elevated dopamine level causes a downregulation of the dopamine transporters, which results in an increased presynaptic reuptake of dopamine, whereby less dopamine is available to the postsynapse in the synaptic cleft), or a consequence of an excessive dopamine level in the PFC, as this results in a reduced dopamine level in the striatum. A permanently low dopamine level in the striatum is likely to cause an increase in DAT as a counter-reaction to upregulation. It is also conceivable that the reduced dopamine level in the striatum is the cause that once made THC interesting for addicts. Heinz answers this for alcohol addicts in the direction of both and, although the connections are infinitely more complex.⁴²
  However, it should be noted that cannabinoids are dopaminergic drugs and that ADHD sufferers also have a far above-average affinity for nicotine and alcohol, which also have a dopaminergic effect.
• THC is an established medication for Tourette’s syndrome.⁴³ Tourette’s is a very common comorbidity of ADHD.
• Individual sufferers report that “regular” low THC use significantly reduces their risk of migraines. Migraines are a common comorbidity of ADHD.

We know of several patients who were able to largely resolve severe ADHD symptoms with severe comorbid disorders (including bipolar) with cannabinoid medication (medical hash) - better than with stimulants and other medication. (Private prescription, not reimbursed by health insurance; €130 / month; as of fall 2017).
More and more doctors are now aware of the medical benefits of prescribing THC for ADHD sufferers for whom other medications have been unsuccessful and are willing to prescribe it.

For more on THC-containing medication for ADHD, see*⇒* Medicinal cannabis for ADHD in the section ⇒ Suitable medication for ADHD in the chapter ⇒ Treatment and therapy.

2.4. ADHD symptom improvement through microdosing¶

The above thesis of HPA axis shutdown by THC-mediated massive stress-induced cortisol increase (at least as the sole mode of action) is contradicted by the fact that those affected (including those of the ADHD-I subtype) report a significant improvement in symptoms by microdosing THC or cannabidiol.

Microdosing means a dosage so low that (cumulatively)

• No noise sensation occurs
• Short-term memory is not impaired
• No performance impairment / fatigue occurs.

Several sufferers report that microdosing cannabinoids / cannabidiol - usually using a vaporizer - significantly increases their focus. If short-term memory is impaired, it is reported that an even lower dosage can improve this.
It is also reported that the optimal mixing ratio between cannabinoids and cannabidiol varies from individual to individual and that the degree of symptom improvement is influenced by the individual adjustment of the mixing ratio. A very low proportion of cannabidiol was reported to be beneficial.

These instructions are not a recommendation for self-medication!
According to §§ 29 ff. BtMG, unauthorized cultivation, production, trade, import, export, sale, disposal, other placing on the market, acquisition and possession of all parts of the cannabis plant are punishable in Germany.

The basic principle of microdosing can be scientifically regarded as the difference between a drug (high dosage leads to intoxication) and a medication (low dosage remedies a deficit). This principle is exactly what is known to make the difference between amphetamine as a drug or as a medication (e.g. for ADHD).
However, amphetamine drugs or amphetamine-related drugs, which are widely used for ADHD, are subject to multiple reviews and very precise dosing due to medical approval procedures. This is not possible with natural substances, so there is always a risk of incorrect dosing.
For this reason, self-medication is generally not advisable, regardless of the legal issues that may arise.

It should also be noted that the alleged medical use sometimes serves merely as a sham argument for concealing drug abuse.

If the usual medication for ADHD (amphetamine medication, methylphenidate, guanfacine, atomoxetine, bupropion, nicotine) does not help sufficiently, medical cannabis can be prescribed by a doctor. It is known that in some cases this is the most effective treatment for ADHD.
Medicinal cannabis has a defined active ingredient content (which is measured and documented batch by batch) and can therefore be dosed precisely.
The explanation of microdosing is informative for this area of application.

3. Amphetamines / Mesamphetamines¶

Amphetamine drugs can significantly reduce stress levels. However, abuse of amphetamine drugs leads to an increased stress response in the long term.⁴⁴
Meprobromat, a tranquilizer from the 1960s (now illegal due to its addictive potential), reduces the adrenaline rush under stress.⁴⁵
“Crystal meth” is a mesamphetamine and is very similar to the mode of action of amphetamine as an ADHD medication.⁴⁶
It has been reported that the use of illegal substances such as cocaine and amphetamines can have a positive effect on concentration deficits (“self-medication”).⁴⁷
It goes without saying that this cannot provide legal justification. However, it will have to be taken into account in the context of the question of guilt (severity of guilt), which cannot prevent a penalty, but can possibly mitigate it.

4. Cocaine¶

Cocaine inhibits the reuptake transporters of dopamine, noradrenaline and serotonin.

5. Alcohol¶

• Alcohol increases the dopamine level
  • In the PFC⁴⁸
  • In the striatum⁴⁸
• Alcohol significantly increases adrenaline levels for at least 12 hours after ingestion of moderate amounts of alcohol (1.43 g/kg body weight). The noradrenaline level is significantly increased, especially in the first 6 hours, and tends to increase thereafter.⁴⁹
• Excessive alcohol consumption can increase adrenaline and norrenaline levels for up to one week. Increased levels of 17-hydroxycorticosteroid were also found. 0.5 g of chloromethiazole reduced catecholamine levels.⁵⁰

6. LSD¶

Microdoses of LSD (100 nanograms/kg and less) appear to increase serotonin levels, while even slightly higher doses cause a decrease in serotonin.⁵¹

An online survey revealed a significantly higher subjective effect strength of microdosing with psychedelic substances such as LSD than a conventional treatment for psychological and physiological diagnoses, especially for⁵²

• ADHD
• Anxiety disorders
• Autism spectrum disorders (ASD) (not significant here, however)
• Personality disorders (not significant here, however).

In contrast, higher doses with a regular psychedelic effect were judged to be better than microdosing at

• Depression
• Anxiety.

No significant difference was found for

• Physiological disorders.

Another study reported fewer side effects with microdosing of LSD (10 micrograms of LSD every third day was tested in more than 1000 subjects with a wide range of disorders over 18 months) compared to conventional treatment.⁵³