Cannabis is traditionally derived from the plant Cannabis Sativa. The dried buds and accompanying leaves of cannabis are most commonly smoked, ingested and or vaped [17].  Onset of physiologic and psychologic effects vary based on route of administration, with peak effects occurring 30 minutes after inhalation and 2 to 4 hours after ingestion. Physiologic effects include tachycardia, hypertension, dry mouth and conjunctival injection. Acute effects include on the one hand relaxation, euphoria, heightened perception, sociability, sensation of time slowing, increased appetite and decreased pain, and on the other hand paranoia, anxiety, irritability, impaired short term memory, poor attention and judgement, and poor coordination and balance [18,19].

The mechanism for any potential therapeutic effects of cannabinoids (CBD) in ADHD is unknown. One possibility is that cannabinoids enhance dopaminergic transmission which is thought to be the main mechanism by which stimulants decrease ADHD symptoms and improve cognitive performance [20,21].  In addition to dopamine, the role of glutamate, GABA, and other transmitter systems need consideration, as well as N-methyl-D-aspartate and cannabinoid 2 (CB2) receptors, which has been suggested to modulate impulsivity in interaction with endocannabinoids [22-24].

Thirty eight percent (38%) of participants in a large multisite study of adolescent cannabis users met diagnostic criteria for ADHD [25].  A recent systematically review the scientific literature to characterize the effects of cannabis use on brain structure, function, and neurodevelopmental outcomes in adolescents and young adults with ADHD identified 11 studies. The limited, potentially underpowered evidence does not support the hypothesis that cannabis use has a deleterious impact on neuropsychological tasks in transitional age youth with ADHD [26].

There is only one controlled study on cannabis-based medication in ADHD. This was a formal clinical trial in the UK treating a small number of adult ADHD patients with the Satinex Oromucosal SprayR, containing a 1:1 ratio of Delta-THC to cannabidiol. The study found that despite there being no statistically significant difference in the primary outcome of cognitive performance and activity level measured by QbTest, the overall trend was that the active group (n=15) achieved better results than the placebo group (n= 15) and reported reduced hyperactivity/impulsivity symptoms as well as improved emotional lability [12].  The absence of any negative effect on cognitive performance is of potential interest given that cannabis use is generally associated with impaired cognitive function. A further trial to test negative effect on cognitive performance would require a longer follow-up period to test this. The researchers reported one serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problem) adverse event in the placebo group [12].

A large cross-sectional study involving 2811 adults, aged between 18- 74, all of them were cannabis users but with different regimes, showed an association between the frequent use of cannabis and the subtype of ADHD. A greater proportion of affected daily users reported meeting symptom criteria for the combined/hyperactive-impulsive subtype of ADHD rather than the inattentive type. Casual or moderate users showed no significant difference in meeting symptom criteria of an ADHD diagnosis. The authors speculated that cannabis might cause frontal dysregulation, which is more typical in combined type ADHD that includes hyperactive-impulsive symptoms [11].

In a cross-sectional questionnaire-based study on adult patients who were licensed for medical cannabis use and also were diagnosed with ADHD, it was revealed that the high dose consumption of medicinal cannabis components (phytocannabinoids and terpenes) was associated with ADHD medication reduction. In addition, the higher dosage of CBD was associated with a lower Adult ADHD Self Report Scale-ASRS)- Rating Score.  No significant differences in Mental illnesses, co-morbidities were found between the low and high medicinal cannabis. It was speculated that some constitutes of the cannabis plant contribute more than others to its neurobiological effect and for this reason, ADHD patients consume MC as a substitute treatment for their conventional ADHD treatment [27].

In a longitudinal study inviting 73 participants, Functional Magnetic Resonance Imaging (fMRI) from young adults with childhood ADHD (no= 25) and without (no= 25) cannabis use was compared with a control normative comparison group (n= 11 cannabis users) and without (n=12) cannabis use was completed. ADHD participants made significantly more commission errors on NOGO trials than controls.  ADHD participants also had less fronto-parietal and fronto-striatal activity, independent of cannabis use.  An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and40 cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition.  The cannabis use was associated with hippocampal and cerebral activation, areas rich in cannabinoid receptors, in local normative comparison group but not with the ADHD participants. However, the sample was disproportionately male, hence results may not generalise to female cannabis users. Hence behavioural impairments from chronic cannabis use might be more evident in real-world situations that do not elicit unusual vigilance or attention [28].

An observational descriptive study, including 18 patients with an average age 10 years old concluded that there was improvement in the symptoms of social communication and many co-morbid mental disorders in patients [; with ASD including symptoms of ADHD. Behaviour disorders, motor deficits, autonomy deficits, communication and social interaction, cognitive deficits, sleep disorders and seizures, with very infrequent and mild adverse effects such as sleepiness, irritability, diarrhoea, conjunctival hyperaemia and increased body temperature [29].  Another single case study of 6 years old boy with autism and ADHD type symptoms, was treated with daily dronabinol for six months and was noted to have improvement in hyperactivity, irritability, lethargy, stereotyped behaviours and speech , as measured by Aberrant Behavior Checklist (ABC) [30].

A cross sectional case control study of brain Network structure and organization on synthetic cannabis users with and without ADHD in adolescents. Twenty-seven cannabis users (14 without ADHD and 13 with ADHD combined type) with a history of using synthetic cannabis more than three times a week for at least 6 months prior to study enrolment were included in the study along with 13 controls. Patients were abstinent for at least 2 days before having diffusion- weighted Magnetic Resonance Imaging Scanning. The authors found that Synthetic cannabis users without ADHD had significantly weaker connectivity compared to controls in bilateral hemispheres. In contrast, synthetic cannabis users with ADHD showed stronger structural connectivity compared to controls. In addition, adolescent cannabis users with ADHD displayed reduced network organisation, suggesting that poor structural network segregation and preserved structural network integration. These results suggest that comorbidity of ADHD and substance dependence may show different structural connectivity alterations than substance use alone [31].

Literature review on the cannabis use among children including those with developmental and behaviour problems such as ADHD and ASD concluded that cannabis can’t be safely recommended for the treatment of developmental or behaviour disorders. The authors addressed those studies conducted by the advocate groups on the use of cannabis for paediatric therapeutic use do not provide enough evidence on effectiveness, safety and tolerability. It is therefore important for all parties to be aware of the long-term hazards or regular cannabis use when using marijuana for medicinal purposes [17].

A longitudinal study in New Zealand children showed a clear dose-dependent association between ADHD symptoms at age of 25 years and cannabinoid abuse.  This association was found to be mediated through abuse of other substances, including Ectasy (MDMA) and methamphetamines, suggesting the possible existence of a causal chain process in which cannabis use led to increased rates of other forms of drug use, with these being associated with increased symptoms of adult ADHD [32].

In a recent observational cohort survey in the UK, it was identified that families of children with ADHD are using a wide variety of main and nonmain treatments, which are both publicly and privately funded   to help with ADHD management. Nearly 70% of those surveyed reported using pharmaceutical medications, 74% had participated in a parenting class and 45% reported use of non-mainstream treatment. The most popular non-mainstream treatments used were nutrition, homoeopathy, massage and cranial osteopathy.  Out of 175 families surveyed there was only one child who m ADHD symptoms were managed by cannabidiol [33].

The therapeutic use of cannabinoids for a 33 years old male with combined- type adult ADHD patient who accessed Bedrocan^R and Bediol^R for more than 5 years was described in detail. The patient reported relief for his ADHD symptoms, with reduced hyperactivity as well as improved focus, impulse control and better frustration control. Before using cannabinoids, the patient was tried for several years on several medications to Ritalin, Temazepam, Bupropion and Alprazolam but with poor results and hence he was tried on Cannabinoids [34].

In a series of clinical cases with 30 treatment- resistant adults with ADHD, it was found that medical cannabis was helpful for a variety of symptoms, including improved concentration and sleep as well reduced impulsivity. Seventy three percent preferred to use only cannabinoids after the study, while 27% (No: 8) continued to combine CBD with other stimulant medications [35].

In a single case study of a cannabis using, 28 adult males with ADHD off stimulants, the subject’s driving skills in a simulated test during a time of abstinence improved after smoking marijuana. It was also reported that the consumption of cannabis had a positive impact on performance, behaviour and mental state of the subject. However, on blood testing, very high concentrations of cannabinoids were found in view of the patient smoking cannabis instead of taking the prescribed dronabinol [36].

On the other hand, the research on cannabinoid oil and other cannabis products as a possible intervention for ADHD does not show effectiveness for managing symptoms, but actually shows increased mental and physical health risks. There haven’t been studies on long term effects. While some people are using it and have shared their results publicly, researchers and medical professionals have not found evidence that it is an effective treatment for ADHD. The research does not show that CBO oil works for ADHD management [37].

Given the increasing prevalence of adolescent cannabis misuse and dependence as well as the growing body of literature linking cannabis use to long term and potentially irreversible adverse physical, neurocognitive, psychiatric and psychosocial outcomes, it is now more important than ever for the developmental-behaviour paediatrician to understand the available evidence on cannabis. Large professional organisations , including the American Academy of Paediatrics, The American Medical Association, the American Society of Addiction Medicine, and the American Academy of Child and Adolescent  Psychiatry all have policy statements  identifying marijuana use as a public health concern  and currently oppose further steps toward legalisation [17].