Skip to main content
ADxS.org

Cannabinoids for ADHD and Stress

Cannabinoids for ADHD and Stress

Last updated:

1. The Endocannabinoid System and ADHD

Cannabinoid-1 receptors (CB1R) could be a useful target in the treatment of ADHD.1

1.1. CB1R reduced at SHR

SHR shows a significantly reduced basal level of CB1R gene and protein expression in the brainstem.234
Another study found elevated receptor gene expression levels in an animal model of ADHD.5

A CB1R agonist also reduced your choice impulsivity (delay aversion).3
Amphetamine loses its dopamine- and norepinephrine-enhancing effects when the CB1R is blocked.6 We are considering whether a deficiency in CB1R could be a possible cause of AMP nonresponsiveness.

It is unclear how this is consistent with a study conducted on SHR that found that inhibiting CB1R in the PVN could lower blood pressure.7

Chronic administration of methylphenidate (MPH) at therapeutic doses reduced CB1R levels in rats after 4 weeks, whereas administration at recreational doses increased them.8

The synthetic CB2R agonist (and, to a lesser extent, CB1R agonist) WIN55,212-2 (WIN) induced a conditioned place preference in both adolescent and adult SHR rats, whereas in Wistar control animals, it induced a conditioned place aversion only in adults. The behavioral effects of WIN were mediated via the CB1R. The contrasting effects of WIN in Wistarand SHR rats, as well as the greater resistance of adolescent rats to the aversive and rewarding effects of WIN, suggest that both adolescence and the ADHD-like profile of SHR rats are factors that influence the motivational properties of cannabinoids.9
WIN (0.25 and 1.25 mg/kg i.p.) promoted locomotor activity in the open field only in adolescent SHR, but not in adult SHR or in adolescent or adult Wistar control rats. Pretreatment with the selective CB1R antagonist AM 251 (0.25 mg/kg, i.p.) prevented this effect in adolescent SHR.10

A study found that acute activation of CB1R and CB2 in SHR5

  • increased risky behavior and hyperactivity in adolescence, particularly in female rats
  • risk assessment worsened in adulthood, while hyperactivity remained unchanged

In contrast, chronic activation of CB1R or CB2R did not alter hyperactivity, risk-taking behavior, or working memory in SHR.11

1.2. CB1 Receptor and Impulsivity

Reduced CB1R levels were found in SHR (the primary model animal for ADHD). A CB1R agonist simultaneously reduced choice impulsivity (delay aversion) in these mice.3
In contrast, another study found that a CB1R antagonist reduced choice impulsivity, while a CB1R agonist increased it.12
THC, a CB1R agonist, increased some, but not all, forms of impulsivity in humans.13
The CB1R antagonist rimonabant (SR141716A) reduced behavioral impulsivity in rats, while the agonist WIN55,212-2 only slightly increased it and had no effect on choice impulsivity.14

Daily cannabis use is more common among people with ADHD-HI, that is, those with hyperactivity and impulsivity.15 This is consistent with data from the ADxS symptom test, in which approximately 650 participants answered a question about frequent cannabis use. Positive responses correlated with hyperactivity and impulsivity.

The effect of endocannabinoids on hyperactivity appears to have inverted U-shaped consequences.

Mice with traumatic brain injury exhibited increased hyperactivity, which correlated with reduced levels of ethanolamide endocannabinoids (AEA, OEA, PEA) in the perilesional and ipsilateral subcortical brain tissue.16

1.3. CB2 Receptor and Hyperactivity/Impulsivity

DAT-CNR2 mice lack cannabinoid-2 receptors (CB2R) on dopaminergic neurons in the midbrain.
DAT-CNR2 mice show:17

  • Hyperactivity (both males and females)
  • Impulsivity in decision-making
  • reduced anxiety-related behavior
  • increased risk-taking behavior

Amphetamine at a therapeutic dose (2 mg/kg) reduces hyperactivity and ADHD symptoms. This is consistent with the typical paradoxical effect of stimulants in ADHD.

A study found elevated receptor gene expression levels in an animal model of ADHD.5

Postnatal administration of the CB1 receptor antagonist/inverse agonist rimonabant (SR141716A)—which also binds to CB2R at high doses—to newborn Sabra mice resulted in:18

  • in males
    • vocal tics
    • Learning Disabilities
    • excessive vocalization
    • Hyperactivity
    • motor tics
    • risky behavior in adulthood (at 5 mg, but not at 10 mg)
    • Pre-pulse inhibition remains unchanged at 5 and 10 mg, but changes at 20 mg

In CB1 knockout mice, administration of rimonabant to newborn Sabra mice resulted in:18

  • in females
    • Standing up (a sign of hyperactivity)
    • Reduced physical activity
    • Risky behavior in adulthood
    • Grooming remains unchanged

In CB2 knockouts, rimonabant may act solely as an inverse agonist of the CB1 receptor, thereby increasing dopamine release. In Sabre-CB2 knockouts, administration of rimonabant resulted in:18

  • in males
    • Hyperactivity at 4 and 8 weeks of age (from 6 weeks onward = adulthood)
    • No learning difficulties at 5 mg
    • Unchanged grooming
    • No voice-like tics at 5 mg
      • Voice-like tics may therefore depend on functional CB2 receptors
  • in females
    • Do not stand up
    • Physical activity patterns remain unchanged
    • no vocal tics
    • Grooming remains unchanged
    • High-risk behavior remains unchanged in adulthood

In females, CB2R therefore appears to control vertical hyperactivity and risky behavior, while CB1R regulates horizontal hyperactivity and motor activity.

In C57BL/6J mice, 5 mg of rimonabant caused;18

  • in males
    • Voice-like tics occur only when mothers have a suboptimal diet
      • not in females
    • No voice-like tics when mothers have an optimal diet

1.4. Preventing Sensory Overload

Endocannabinoids (the body’s own cannabinoids) bind to CB1R and, among other things, help protect against sensory overload.19

1.5. Attention and Distractibility

The AEA degradation inhibitor URB597 improved attention and reduced distractibility in healthy mice.20

1.6. Anandamide (AEA) Levels Are Elevated in ADHD

Measuring AEA requires a fairly large blood sample—12 ml21.22. A more recent method appears to require smaller volumes.23 Nevertheless, peripheral endocannabinoid concentrations depend heavily on the conditions under which samples are collected and processed. Due to the instability of endocannabinoid concentrations in blood, strict, harmonized protocols for sample collection and processing are required to avoid artificial differences between samples.23
So far, we have not been able to find any laboratories that offer anandamide or 2-AG analysis as a standard service.

Several studies suggest that levels of AEA (and 2-AG) are elevated in ADHD due to a deficiency of FAAH, which breaks down AEA.

In children with ADHD, elevated levels of anandamide (AEA) were found in peripheral blood mononuclear cells due to reduced AEA degradation caused by decreased FAAH activity. The AEA synthase NAPEPLD remained unchanged.2122 Another study also found elevated AEA levels in children with ADHD.24
FAAH deficiency in ADHD selectively altered synaptic glutamate transmission in the striatum, but not that of GABA. This could suggest that ADHD symptoms may be due, at least in part, to a distinct dysregulation of excitatory and inhibitory synaptic transmission in the striatum.22

ADHD is characterized, to a very significant extent, by reduced self-motivation. AEA reduces motivation. For more on this, see AEA reduces reward-seeking behavior in the article “Cannabinoids Regulate Dopamine” in the chapter “Neurological Aspects / Neurotransmitters in ADHD / Cannabinoid System / What Is Regulated by Cannabinoids.”

Organophosphates reduce FAAH, thereby increasing anandamide levels and causing ADHD symptoms in mice.2526

Since endocannabinoids reduce pain perception via the CB1R, the same is true when AEA levels are elevated. An extreme example is the FAAH-KO mouse. In ADHD, however, pain perception is often heightened.

The AEA reuptake inhibitor AM-404 reduced ADHD symptoms in mice.2728 In juvenile SHR mice, AM-404 reduced hyperactivity.29

An increase in anandamide (AEA) resulting from a reduction in AEA breakdown via an FAAH inhibitor normalized blood pressure in SHR.3031
The AEA reuptake inhibitors AM404 and VDM11, as well as the FAAH inhibitor AA5HT, attenuated spontaneous hyperlocomotion in DAT-KO mice.32
Prenatal administration of AM-404 to Naples rats (an ADHD animal model) reduced their hyperactivity by 20%.33

AM-404 (N-(4-hydroxyphenyl)-arachidonylamide) is an AEA reuptake inhibitor3435 , although there are also those who disagree.3637 AM-404 also inhibits FAAH and thus the breakdown of AEA.3835
Both reuptake inhibition and inhibition of the metabolite lead to elevated extracellular levels (in this case, of anandamide (AEA)). At first glance, this appears to contradict the hypothesis of elevated AEA in ADHD, but only if one regards AEA as the causal factor behind the heightened ADHD symptoms. If, on the other hand, the elevated levels of AEA and 2-AG were compensatory or protective responses by the brain in ADHD, this could, in our view, conclusively explain why AEA and 2-AG are elevated in ADHD, why a further increase in AEA reduces ADHD symptoms, and why MPH leads to reduced levels of AEA and 2-AG.

It is possible that AM-404’s effectiveness in treating ADHD symptoms could also be due to other mechanisms of action.
AM-404 acts as an AEA reuptake inhibitor and a weak CB1R and CB2R agonist.39 AM-404 reduced the respiratory rate in wild-type mice while simultaneously lowering arterial oxygen saturation and increasing respiratory dilation. This effect was mediated via CB1R.40

However, AM-404 also acts on several signaling pathways outside of the AEA system.41 AM-404 exerts a stronger effect via TRPV1 receptors than via CB1R.28 The anxiolytic effect of AM-404, as well as that of THC, appears to be mediated via 5-HT1A receptors.42

AM-404 is formed by the deacetylation of acetaminophen to 4-aminophenol (p-aminophenol) in the liver, followed by the conjugation of 4-aminophenol with arachidonic acid by FAAH. AM-404 is a potent activator of TRPV1 and Transient Receptor Potential Ankyrin 1 (TRPA1), as well as a weak agonist of CB1R and CB2R. The activation of these receptors by AM-404 may mediate its analgesic effects.39
Paracetamol is thought to significantly increase endocannabinoid levels through its metabolite AM-40443 and to influence the endocannabinoid pathway44. However, no effect of paracetamol on ADHD symptoms has been reported to date.

A survey on the ADHD-Forum.adxs.org with the question “Has anyone ever noticed an effect of acetaminophen on their ADHD symptoms? Please only participate if you’ve taken acetaminophen since becoming aware of your ADHD symptoms,” and the following 3 options, yielded the following results among 116 participants:

  • 85%: No, acetaminophen did not change my ADHD symptoms
  • 13%: Yes, acetaminophen improved my ADHD symptoms
  • 2%: Yes, acetaminophen made my ADHD symptoms worse

 AM-404 and acetaminophen exhibited dose-dependent antidepressant and anti-compulsive effects comparable to those of fluoxetine and potentiated its effects. Fenclonin (pCPA, a serotonin synthesis inhibitor) reversed these effects of acetaminophen and AM-404. Pretreatment with the CB1R antagonist AM251 attenuated the effects of acetaminophen and AM-404.45

AM-404 has antibacterial activity. AM-404 inhibited the growth and biofilm formation of P. gingivalis via an unsaturated carbon chain. AM-404 was not toxic to the mammalian cells tested. The primary antibacterial mechanism of action of AM-404 appears to be membrane permeabilization.46

Caution: Even at normal doses, acetaminophen can cause liver damage. Research is underway on acetaminophen analogs that provide pain relief via TRPV1 without causing liver damage.47
Therefore, long-term use of acetaminophen is not recommended.

Elevated AEA has also been observed in tic disorders48 and PTSD49.
Endocannabinoid levels are also elevated in obesity.50
In Parkinson’s disease, AEA appears to be elevated, just as 2-AG is.51

No correlation was found between the FAAH gene polymorphism rs324420 (C385A) and ADHD.52

1.7. Elevated 2-AG levels in ADHD

2-AG levels in cerebrospinal fluid correlated with the severity of ADHD symptoms.48

1.8. MPH reduces anandamide and 2-AG

MPH reduces the levels of the endocannabinoids anandamide and 2-AG in the limbic forebrain in a dose-dependent manner. An optimal dose reduced anandamide levels by 30% and 2-AG levels by 45%. At higher doses, anandamide and 2-AG levels rose again.53
The selective dopamine reuptake inhibitor GBR 12909 (1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) also significantly reduced anandamide levels and, to a lesser extent, 2-AG levels.
The D1 receptor antagonist SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) increased anandamide levels and did not alter 2-AG levels.
The D1 receptor agonist SKF 33939 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) reduced anandamide
The D2 receptor antagonist eticloprid significantly increased 2-AG levels and had no effect on anandamide.
The D2 agonist quinpirol at low doses (as preferred by autoreceptors) increased anandamide; higher doses reduced anandamide to levels close to those of controls. Quinpirol did not significantly affect 2-AG.

Endogenous dopamine appears to exert a distinct, inhibitory effect on anandamide and 2-AG levels through the activation of D1 and D2 receptors, exerting a distinct, inhibitory effect on anandamide and 2-AG levels, although the modulation of endocannabinoid levels by dopamine is thought to be secondary to changes in glutamatergic transmission.53

Seven days after administration of methamphetamine at neurotoxic levels, both dopamine levels and the density of dopamine transporters in the limbic forebrain had decreased. CB1R density and CB1R activity were unchanged. The 2-AG level was elevated. MAGL activity was reduced.54

  • CB1R antagonists block amphetamine-induced LTD in the amygdala in a dose-dependent manner.55 This suggests that AMP increases CB1R agonist activity.
    In another study, the amphetamine MDMA unexpectedly did not increase either AEA or 2-AG.56

On the other hand, the endocannabinoid system increases dopamine levels via the CB1R. For more on this, see the section above on CB1R and dopamine.
In ADHD, however, the mechanism of action is unlikely to originate with endocannabinoids. Since anandamide and 2-AG are elevated in ADHD, and both are CB1R agonists, this should increase dopamine levels—both through the CB1R’s effect on GABA and through AEA’s inhibition of DAT. The central problem in ADHD, however, is the reduced dopamine level.

Chronic administration of methylphenidate (MPH) at drug doses resulted in increased CB1R levels in rats after 4 weeks, whereas CB1R levels decreased 4 weeks after chronic low-dose MPH administration.8

1.9. FAAH gene variants moderate the effects of amphetamine

Depending on their FAAH gene variant, healthy participants responded differently to 0, 10, or 20 mg of D-Amp.57

A study found elevated levels of FAAH gene expression in an animal model of ADHD.5

1.10. MAGL in ADHD

A study found elevated levels of FAAH gene expression in an animal model of ADHD.5

2. Endocannabinoids and Stress

2.1. Early-Life Stress Alters CB1R

Stress affects the endocannabinoid system through epigenetic mechanisms.58
Early-life stress resulted in reduced levels of CB1R and FAAH, as well as epigenetic changes in the mPFC of male rats.59 Epigenetic changes were also observed in female rats, but there was no reduction in CB1R and FAAH levels.60

CB1R blockade reversed the otherwise typical decline in neuronal activation in corticostriatal regions in response to repeated stress exposure.61 CB1R-KO mice exhibited an inappropriate behavioral adaptation to repeatedly presented stressors.6263

2.2. Endocannabinoids Regulate Stress

Endocannabinoids play a crucial role in regulating the stress response by modulating the sensitivity and activation of the HPA axis.646566
This regulation occurs primarily via the CB1R.67
Endocannabinoids are also involved in the process of stress adaptation.68

Endocannabinoids significantly inhibit the HPA axis.6970

Stress reduces anandamide (AEA) and CB1R and increases AG-2.71
AEA and AG-2 mediate different adaptive responses to chronic stress:64
After repeated stress, it becomes apparent that:

  • AEA is persistently reduced throughout the entire corticolimbic stress circuit
  • 2-AG levels are elevated, but only in the amygdala, in a stress-dependent manner
  • Inhibition of AEA hydrolysis prevented the development of basal hypersecretion of corticosterone following repeated stress
  • CB1R antagonists administered prior to the final stressor reduced the decline in corticosterone responses triggered by repeated stress

AEA was reduced 30 minutes after acute stress and 24 hours after the last chronic stress (30 minutes daily for 9 days) in:64

  • Amygdala
  • Hypothalamus
  • PFC
  • Hippocampus
  • Thalamus (decrease, but not significant)

Only in the PFC did chronic stress cause an increase in basal corticosterone release accompanied by a decrease in AEA levels.64

AG-2 was elevated 30 minutes after acute stress, but not 24 hours after the last episode of chronic stress (30 minutes daily for 9 days), only in:64

  • Amygdala
  • unchanged, however, in the hypothalamus, prefrontal cortex, hippocampus, and thalamus

The increase in AG2 in the amygdala correlated with a reduced corticosterone response following the most recent chronic stress.64

Chronic stress (30 minutes daily for 9 days) resulted in elevated basal corticosterone levels.64
The CB1R antagonist AM251 did not prevent this increase.
The AEA degradation inhibitor URB597 reduced this increase by half.
The AEA reuptake inhibitor AM-404 prevented the increase.

However, the CB1R antagonist AM251, administered before each daily stressor, prevented the decline in the immediate corticosterone stress response. The AEA degradation inhibitor URB597 and the AEA reuptake inhibitor AM-404 did not prevent this decline.64

The decline in the corticosterone stress response to repeated restraint appears to be mediated by enhanced 2-AG-mediated activation of CB1 receptors in the basolateral amygdala.64

In response to stress, it causes / mediates:71

  • the decline in AEA
    • a manifestation of the stress response
    • Activation of the HPA axis
    • Increase in anxiety-related behavior
  • the 2-AG increase
    • Termination and Adjustment of the HPA Axis
    • Changes in pain perception
    • Changes in memory
    • Changes in synaptic plasticity

CB1R agonists (such as THC) inhibit the HPA axis’s response to stress.72

2.3. Stress affects the endocannabinoid system

Chronic, unpredictable stress causes a downregulation of CB1R and a decrease in 2-AG levels in the hippocampus. Both levels remained unchanged in the frontal lobe.73
Chronic, unpredictable stress leads to symptoms of depression and neuropathic pain, such as

  • thermal hyperalgesia74 and cold allodynia75 were correlated with reduced CB1R76 and 2-AG in the hippocampus73, increased CB1R in the PFC76, and reduced dopamine receptors77 in the brain.78

Both acute stress and chronic (10-day) restraint stress increase FAAH, which breaks down AEA, and reduce AEA levels.798081
The extent to which AEA reduces CB1R activation in the basolateral amygdala appears to be the decisive factor in determining the degree to which stress activates the HPA axis and corticosterone release:81

  • A 30-minute restraint stress increases FAAH, which breaks down endocannabinoids, in the amygdala of rats, thereby reducing AEA
  • In stressed rats, amygdala AEA levels were negatively correlated with serum corticosterone
  • Pharmacological inhibition of FAAH in the basolateral amygdala reduced stress-induced corticosterone secretion
    • Concurrent administration of the CB1R antagonist AM251 blocked this
  • Stress-induced corticosterone secretion was
    • significantly reduced by administration of CB1R agonists into the basolateral amygdala, and
    • increased by administration of CB1R antagonists

Social stress appears to suppress the endocannabinoid system in vulnerable individuals, which could further increase the tendency to use cannabis, since CB1R agonists (such as THC) inhibit the HPA stress response.72

THC increased dopamine uptake and dopamine metabolism in the striatum of stressed rats, but not in unstressed rats.8283 84 Cross-sensitization between THC and stress has been reported.85 Subjects at increased risk for schizophrenia exhibited an unchanged dopamine stress response to a psychosocial stress task despite increased positive symptoms and attenuated psychotic symptoms.7286

2.4. Cannabinoids in late adolescence can reverse the damage caused by early childhood stress

The FAAH inhibitor URB597, when administered during late adolescence (P45–60, equivalent to 18 to 25 years of age in humans), eliminated the effects of early childhood stress (reduced social preference, impaired social recognition, increased learned helplessness, and anxiety-like behavior) in rats. When administered during early adolescence, URB597 did not reverse these effects.87 In the mPFC, early-life stress downregulated miR-16 in males and miR-135a in females, an effect that URB597 reversed when administered during late adolescence. In females, early-life stress caused increased CB2R and decreased FAAH in the mPFC. Administration of URB597 during late adolescence also reversed these effects.88

Early-life stress led to impaired short-term memory performance in adult male and female rats on tasks involving spatial localization and social recognition. In males, the recognition of new objects was also impaired. The synthetic CB2R agonist (and, to a lesser extent, CB1R agonist) WIN55,212-2, administered during late adolescence (corresponding to 18 to 25 years of age in humans), prevented these stress-induced impairments and reduced anxiety. In females, WIN normalized the early-childhood-stress-induced upregulation of glucocorticoid receptors in the PFC and CB1R in CA1. In males, WIN normalized the early-life stress-induced upregulation of glucocorticoid receptors in the PFC and downregulation of CB1R in the basolateral amygdala.89

Early-life stress can increase susceptibility to depression. Male and female rats that had been exposed to early-life stress were injected with the FAAH inhibitor URB597 or the MAGL inhibitor JZL184 for two weeks during late adolescence (P45–60). FAAH and MAGL inhibitors administered during late adolescence prevented:90

  • depression- and anxiety-like behavior in males and females induced by early-life stress
  • the impairment of social behavior and neural plasticity in males and females
  • Changes in MAGL activity induced by early-life stress in the hippocampus of males and in the hippocampus and nucleus accumbens of females
  • changes in BDNF levels induced by early-life stress in the hippocampus and nucleus accumbens of males and in the hippocampus of females

Another study on URB597 found similar results.91

Escitalopram at PT 35 to 55 alleviated anxiety and despair-like behavior in rats that had experienced early-life stress due to maternal withdrawal by altering the gene expression of CB1R, among other genes.92

THC93, CBD9495 , and a CB1R antagonist95 administered during puberty reversed the increased CB1R, DRD2, and DRD3 expression in the PFC of rats that were prenatally treated with methylazoxymethanol acetate (MAM), as well as the resulting behavioral changes. Prenatal MAM causes brain developmental abnormalities that lead to symptoms of schizophrenia.96

  1. Castelli M, Federici M, Rossi S, De Chiara V, Napolitano F, Studer V, Motta C, Sacchetti L, Romano R, Musella A, Bernardi G, Siracusano A, Gu HH, Mercuri NB, Usiello A, Centonze D (2011): Loss of striatal cannabinoid CB1 receptor function in attention-deficit / hyperactivity disorder mice with point-mutation of the dopamine transporter. Eur J Neurosci. 2011 Nov;34(9):1369-77. doi: 10.1111/j.1460-9568.2011.07876.x. PMID: 22034972. ↥

  2. Haspula D, Clark MA (2016): Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats. J Neurochem. 2016 Nov;139(4):523-536. doi: 10.1111/jnc.13776. PMID: 27529509. ↥

  3. Adriani W, Laviola G (2004): Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model. Behav Pharmacol. 2004 Sep;15(5-6):341-52. doi: 10.1097/00008877-200409000-00005. PMID: 15343057. REVIEW ↥ ↥ ↥

  4. Haspula D, Clark MA (2017): MAPK activation patterns of AT1R and CB1R in SHR versus Wistar astrocytes: Evidence of CB1R hypofunction and crosstalk between AT1R and CB1R. Cell Signal. 2017 Dec;40:81-90. doi: 10.1016/j.cellsig.2017.09.002. PMID: 28887229. ↥

  5. Penna DBS, Gumiéro Costa S, Romão JS, da Costa Calaza K, de Jesus Oliveira K, Dos Santos Rodrigues A, Pandolfo P (2025): Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model. Pharmacol Biochem Behav. 2025 Mar;248:173969. doi: 10.1016/j.pbb.2025.173969. PMID: 39922504. ↥ ↥ ↥ ↥ ↥

  6. Kleijn J, Wiskerke J, Cremers TI, Schoffelmeer AN, Westerink BH, Pattij T (2012): Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation. Neurochem Int. 2012 Jun;60(8):791-8. doi: 10.1016/j.neuint.2012.03.002. PMID: 22426202. ↥

  7. Gao HL, Yang Y, Tian H, Fu LY, Liu KL, Jia XY, Shi XL, Kang YM, Yu XJ (2025): Inhibition of CB1R in the Hypothalamic Paraventricular Nucleus Ameliorates Hypertension Through Wnt/β-Catenin/RAS Pathway. Cardiovasc Toxicol. 2025 Jan;25(1):9-23. doi: 10.1007/s12012-024-09938-2. PMID: 39467886. ↥

  8. Connor C, Hamilton J, Robison L, Hadjiargyrou M, Komatsu D, Thanos P (2022): Abstinence from Chronic Methylphenidate Exposure Modifies Cannabinoid Receptor 1 Levels in the Brain in a Dose-dependent Manner. Curr Pharm Des. 2022;28(4):331-338. doi: 10.2174/1381612827666210127120411. PMID: 33504296. ↥ ↥

  9. Pandolfo P, Vendruscolo LF, Sordi R, Takahashi RN (2009): Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder. Psychopharmacology (Berl). 2009 Aug;205(2):319-26. doi: 10.1007/s00213-009-1542-3. PMID: 19407992. ↥

  10. Pandolfo P, Pamplona FA, Prediger RD, Takahashi RN (2007): Increased sensitivity of adolescent spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder, to the locomotor stimulation induced by the cannabinoid receptor agonist WIN 55,212-2. Eur J Pharmacol. 2007 Jun 1;563(1-3):141-8. doi: 10.1016/j.ejphar.2007.02.013. PMID: 17374533. ↥

  11. Bussinger de Souza Penna D, Gumiéro Costa S, Davis MP, da Costa Calaza K, Dos Santos Rodrigues A, Pandolfo P (2025): Chronic modulation of endocannabinoid receptors does not impact hyperactivity, risk behavior, and working memory in an animal model of attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav. 2025 Sep;254:174059. doi: 10.1016/j.pbb.2025.174059. PMID: 40617332. ↥

  12. Leffa, Ferreira, Machado, Souza, Rosa, de Carvalho, Kincheski, Takahashi, Porciúncula, Souza, Cunha, Pandolfo (2019): Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder. Eur J Neurosci. 2019 Jun;49(12):1673-1683. doi: 10.1111/ejn.14348. PMID: 30667546. ↥

  13. McDonald J, Schleifer L, Richards JB, de Wit H (2003): Effects of THC on behavioral measures of impulsivity in humans. Neuropsychopharmacology. 2003 Jul;28(7):1356-65. doi: 10.1038/sj.npp.1300176. PMID: 12784123. ↥

  14. Pattij T, Janssen MC, Schepers I, González-Cuevas G, de Vries TJ, Schoffelmeer AN (2007): Effects of the cannabinoid CB1 receptor antagonist rimonabant on distinct measures of impulsive behavior in rats. Psychopharmacology (Berl). 2007 Jul;193(1):85-96. doi: 10.1007/s00213-007-0773-4. PMID: 17387457; PMCID: PMC1915592. ↥

  15. Loflin M, Earleywine M, De Leo J, Hobkirk A (2014): Subtypes of attention deficit-hyperactivity disorder (ADHD) and cannabis use. Subst Use Misuse. 2014 Mar;49(4):427-34. doi: 10.3109/10826084.2013.841251. PMID: 24093525. n = 2.811 ↥

  16. Vogel A, Wilken-Schmitz A, Hummel R, Lang M, Gurke R, Schreiber Y, Schäfer MKE, Tegeder I (2020): Low brain endocannabinoids associated with persistent non-goal directed nighttime hyperactivity after traumatic brain injury in mice. Sci Rep. 2020 Sep 10;10(1):14929. doi: 10.1038/s41598-020-71879-x. PMID: 32913220; PMCID: PMC7483739. ↥

  17. Canseco-Alba A, Sanabria B, Hammouda M, Bernadin R, Mina M, Liu QR, Onaivi ES (2022): Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder. Front Psychiatry. 2022 Feb 8;12:803394. doi: 10.3389/fpsyt.2021.803394. PMID: 35211038; PMCID: PMC8860836. ↥

  18. Gorberg V, Harpaz T, Shamir EN, Karminsky OD, Fride E, Pertwee RG, Greig IR, McCaffery P, Anavi-Goffer S (2025): A Tourette Syndrome/ADHD-like Phenotype Results from Postnatal Disruption of CB1 and CB2 Receptor Signalling. Int J Mol Sci. 2025 Jun 24;26(13):6052. doi: 10.3390/ijms26136052. PMID: 40649832; PMCID: PMC12249578. ↥ ↥ ↥ ↥

  19. Gießen (2007): Endocannabinoide als Schutz vor Reizüberflutung, Pharmazeutische Zeitung, 27.04.2007 german ↥

  20. Contarini G, Ferretti V, Papaleo F (2019): Acute Administration of URB597 Fatty Acid Amide Hydrolase Inhibitor Prevents Attentional Impairments by Distractors in Adolescent Mice. Front Pharmacol. 2019 Jul 19;10:787. doi: 10.3389/fphar.2019.00787. PMID: 31379568; PMCID: PMC6658611. ↥

  21. Centonze D, Bari M, Di Michele B, Rossi S, Gasperi V, Pasini A, Battista N, Bernardi G, Curatolo P, Maccarrone M (2009): Altered anandamide degradation in attention-deficit/hyperactivity disorder. Neurology. 2009 Apr 28;72(17):1526-7. doi: 10.1212/WNL.0b013e3181a2e8f6. PMID: 19398708. n = 30 ↥ ↥

  22. Centonze D, Battistini L, Maccarrone M (2008): The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases. Curr Pharm Des. 2008;14(23):2370-42. doi: 10.2174/138161208785740018. PMID: 18781987. REVIEW ↥ ↥ ↥

  23. Pastor A, Farré M, Fitó M, Fernandez-Aranda F, de la Torre R (2014): Analysis of ECs and related compounds in plasma: artifactual isomerization and ex vivo enzymatic generation of 2-MGs. J Lipid Res. 2014 May;55(5):966-77. doi: 10.1194/jlr.D043794. PMID: 24610889; PMCID: PMC3995474. ↥ ↥

  24. Brunkhorst-Kanaan N, Trautmann S, Schreiber Y, Thomas D, Kittel-Schneider S, Gurke R, Geisslinger G, Reif A, Tegeder I (2021): Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder. Biomedicines. 2021 Sep 6;9(9):1173. doi: 10.3390/biomedicines9091173. PMID: 34572359; PMCID: PMC8467584. n = 169 ↥

  25. Ito Y, Tomizawa M, Suzuki K, Shirakawa Y, Ono H, Adachi K, Suzuki H, Shimomura K, Nabeshima T, Kamijima M (2020): Organophosphate Agent Induces ADHD-Like Behaviors via Inhibition of Brain Endocannabinoid-Hydrolyzing Enzyme(s) in Adolescent Male Rats. J Agric Food Chem. 2020 Feb 26;68(8):2547-2553. doi: 10.1021/acs.jafc.9b08195. PMID: 31995978. ↥

  26. Terajima T, Inoue H, Shimomura K, Iwasaki F, Sasaki A, Ito Y, Kamijima M, Tomizawa M (2023): Organophosphate agent action at the fatty acid amide hydrolase enhancing anandamide-induced apoptosis in NG108-15 cells. J Toxicol Sci. 2023;48(7):421-428. doi: 10.2131/jts.48.421. PMID: 37394655. ↥

  27. Giuffrida A, Beltramo M, Piomelli D (2001): Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology. J Pharmacol Exp Ther. 2001 Jul;298(1):7-14. PMID: 11408519. REVIEW ↥

  28. Rawls SM, Ding Z, Cowan A (2006): Role of TRPV1 and cannabinoid CB1 receptors in AM 404-evoked hypothermia in rats. Pharmacol Biochem Behav. 2006 Apr;83(4):508-16. doi: 10.1016/j.pbb.2006.03.011. PMID: 16647109. ↥ ↥

  29. Beltramo M, de Fonseca FR, Navarro M, Calignano A, Gorriti MA, Grammatikopoulos G, Sadile AG, Giuffrida A, Piomelli D (2000): Reversal of dopamine D(2) receptor responses by an anandamide transport inhibitor. J Neurosci. 2000 May 1;20(9):3401-7. doi: 10.1523/JNEUROSCI.20-09-03401.2000. PMID: 10777802; PMCID: PMC6773117. ↥

  30. Bátkai S, Pacher P, Osei-Hyiaman D, Radaeva S, Liu J, Harvey-White J, Offertáler L, Mackie K, Rudd MA, Bukoski RD, Kunos G (2004): Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation. 2004 Oct 5;110(14):1996-2002. doi: 10.1161/01.CIR.0000143230.23252.D2. PMID: 15451779; PMCID: PMC2756479. ↥

  31. Godlewski G, Alapafuja SO, Bátkai S, Nikas SP, Cinar R, Offertáler L, Osei-Hyiaman D, Liu J, Mukhopadhyay B, Harvey-White J, Tam J, Pacak K, Blankman JL, Cravatt BF, Makriyannis A, Kunos G (2010): Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in hypertension without adverse metabolic effects. Chem Biol. 2010 Nov 24;17(11):1256-66. doi: 10.1016/j.chembiol.2010.08.013. PMID: 21095576; PMCID: PMC3003779. ↥

  32. Tzavara ET, Li DL, Moutsimilli L, Bisogno T, Di Marzo V, Phebus LA, Nomikos GG, Giros B (2006): Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Biol Psychiatry. 2006 Mar 15;59(6):508-15. doi: 10.1016/j.biopsych.2005.08.019. PMID: 16199010. ↥

  33. Viggiano D, Ruocco LA, Pignatelli M, Grammatikopoulos G, Sadile AG (2003): Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples High Excitability rats. Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):129-39. doi: 10.1016/s0149-7634(03)00015-0. PMID: 12732229. ↥

  34. Tóth VE, Fehér Á, Németh J, Gyertyán I, Zádori ZS, Gyires K (2018): Modulation of central endocannabinoid system results in gastric mucosal protection in the rat. Brain Res Bull. 2018 May;139:224-234. doi: 10.1016/j.brainresbull.2018.02.012. PMID: 29438780. ↥

  35. Scienza-Martin K, Lotz FN, Zanona QK, Santana-Kragelund F, Crestani AP, Boos FZ, Calcagnotto ME, Quillfeldt JA (2022): Memory Consolidation Depends on Endogenous Hippocampal Levels of Anandamide: CB1 and M4, but Possibly not TRPV1 Receptors Mediate AM404 effects. Neuroscience. 2022 Aug 10;497:53-72. doi: 10.1016/j.neuroscience.2022.04.009. PMID: 35436517. ↥ ↥

  36. Gifford AN, Bruneus M, Lin S, Goutopoulos A, Makriyannis A, Volkow ND, Gatley SJ (1999): Potentiation of the action of anandamide on hippocampal slices by the fatty acid amide hydrolase inhibitor, palmitylsulphonyl fluoride (AM 374). Eur J Pharmacol. 1999 Oct 21;383(1):9-14. doi: 10.1016/s0014-2999(99)00609-3. PMID: 10556675. ↥

  37. Chen WC, Huang JK, Cheng JS, Tsai JC, Chiang AJ, Chou KJ, Liu CP, Jan CR (2001): AM-404 elevates renal intracellular Ca(2+), questioning its selectivity as a pharmacological tool for investigating the anandamide transporter. J Pharmacol Toxicol Methods. 2001 May-Jun;45(3):195-8. doi: 10.1016/s1056-8719(01)00148-4. PMID: 11755382. ↥

  38. Coleman RA, Muli CS, Zhao Y, Bhardwaj A, Newhouse TR, Trader DJ (2019): Analysis of chain length, substitution patterns, and unsaturation of AM-404 derivatives as 20S proteasome stimulators. Bioorg Med Chem Lett. 2019 Feb 1;29(3):420-423. doi: 10.1016/j.bmcl.2018.12.030. PMID: 30587447; PMCID: PMC6348054. ↥

  39. Bührer C, Endesfelder S, Scheuer T, Schmitz T (2021): Paracetamol (Acetaminophen) and the Developing Brain. Int J Mol Sci. 2021 Oct 15;22(20):11156. doi: 10.3390/ijms222011156. PMID: 34681816; PMCID: PMC8540524. REVIEW ↥ ↥

  40. Iring A, Hricisák L, Benyó Z (2017): CB1 receptor-mediated respiratory depression by endocannabinoids. Respir Physiol Neurobiol. 2017 Jun;240:48-52. doi: 10.1016/j.resp.2017.02.011. PMID: 28254562. ↥

  41. Meneses CCB, Pizzatto LN, Sipert CR, Diogenes A (2021): Endocannabinoids Regulate Stem Cells of the Apical Papilla via a Cannabinoid Receptor and TRPV1-Independent Mechanism. J Endod. 2021 Oct;47(10):1617-1624. doi: 10.1016/j.joen.2021.07.010. PMID: 34293356. ↥

  42. Braida D, Limonta V, Malabarba L, Zani A, Sala M (2007): 5-HT1A receptors are involved in the anxiolytic effect of Delta9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague-Dawley rats. Eur J Pharmacol. 2007 Jan 26;555(2-3):156-63. doi: 10.1016/j.ejphar.2006.10.038. PMID: 17116299. ↥

  43. Deshpande LS, DeLorenzo RJ (2011): Acetaminophen inhibits status epilepticus in cultured hippocampal neurons. Neuroreport. 2011 Jan 5;22(1):15-8. doi: 10.1097/WNR.0b013e3283413231. PMID: 21037491; PMCID: PMC3052417. ↥

  44. Abdel Mageed SS, Ammar RM, Nassar NN, Moawad H, Kamel AS (2022): Role of PI3K/Akt axis in mitigating hippocampal ischemia-reperfusion injury via CB1 receptor stimulation by paracetamol and FAAH inhibitor in rat. Neuropharmacology. 2022 Apr 1;207:108935. doi: 10.1016/j.neuropharm.2021.108935. PMID: 34968475. ↥

  45. Manna SS, Umathe SN (2015): Paracetamol potentiates the antidepressant-like and anticompulsive-like effects of fluoxetine. Behav Pharmacol. 2015 Apr;26(3):268-81. doi: 10.1097/FBP.0000000000000104. PMID: 25340977. ↥

  46. Gerits E, Spincemaille P, De Cremer K, De Brucker K, Beullens S, Thevissen K, Cammue BPA, Vandamme K, Fauvart M, Verstraeten N, Michiels J (2017): Repurposing AM404 for the treatment of oral infections by Porphyromonas gingivalis. Clin Exp Dent Res. 2017 Apr 7;3(2):69-76. doi: 10.1002/cre2.65. PMID: 29744181; PMCID: PMC5719815. ↥

  47. Å Nilsson JL, Mallet C, Shionoya K, Blomgren A, Sundin AP, Grundemar L, Boudieu L, Blomqvist A, Eschalier A, Nilsson UJ, Zygmunt PM (2021): Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity. Eur J Med Chem. 2021 Mar 5;213:113042. doi: 10.1016/j.ejmech.2020.113042. PMID: 33257173. ↥

  48. Müller-Vahl KR, Bindila L, Lutz B, Musshoff F, Skripuletz T, Baumgaertel C, Sühs KW (2020): Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome. Neuropsychopharmacology. 2020 Jul;45(8):1323-1329. doi: 10.1038/s41386-020-0671-6. PMID: 32272483; PMCID: PMC7297729. ↥ ↥

  49. Marusak HA, Ely SL, Zundel CG, Gowatch LC, Shampine M, Carpenter C, Tamimi R, Jaster AM, Shakir T, May L, deRoon-Cassini TA, Hillard CJ (2024): Endocannabinoid dysregulation and PTSD in urban adolescents: Associations with anandamide concentrations and FAAH genotype. Psychopharmacology (Berl). 2024 Nov 16. doi: 10.1007/s00213-024-06717-3. PMID: 39547971. ↥

  50. Kim J, Carlson ME, Kuchel GA, Newman JW, Watkins BA (2016): Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice. Int J Obes (Lond). 2016 Jan;40(1):129-37. doi: 10.1038/ijo.2015.135. PMID: 26219414; PMCID: PMC4722239. ↥

  51. Murillo-Rodriguez E, Pastrana-Trejo JC, Salas-Crisóstomo M, de-la-Cruz M (2017): The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. CNS Neurol Disord Drug Targets. 2017;16(4):370-379. doi: 10.2174/1871527316666170223161908. PMID: 28240187. REVIEW ↥

  52. Anvar LH, Alejafar A, Moosavi SE, Charsouei S, Zeynalzadeh N, Fanid LM, Emamalizadeh B, Aydinlou ZH, Vaezi H, Kashefi A, Tomaz C, Nikanfar M, Ahmadalipour A (2023): The study of rs324420 (C385A) polymorphism of the FAAH gene of the endocannabinoid system in patients with epilepsy and ADHD. Epilepsy Res. 2023 May;192:107100. doi: 10.1016/j.eplepsyres.2023.107100. PMID: 37018974. ↥

  53. Patel S, Rademacher DJ, Hillard CJ (2003): Differential regulation of the endocannabinoids anandamide and 2-arachidonylglycerol within the limbic forebrain by dopamine receptor activity. J Pharmacol Exp Ther. 2003 Sep;306(3):880-8. doi: 10.1124/jpet.103.054270. PMID: 12808005. ↥ ↥

  54. Gutierrez-Lopez MD, Llopis N, Feng S, Barrett DA, O’Shea E, Colado MI (2010): Involvement of 2-arachidonoyl glycerol in the increased consumption of and preference for ethanol of mice treated with neurotoxic doses of methamphetamine. Br J Pharmacol. 2010 Jun;160(3):772-83. doi: 10.1111/j.1476-5381.2010.00720.x. PMID: 20590579; PMCID: PMC2931575. ↥

  55. Huang YC, Wang SJ, Chiou LC, Gean PW (2003): Mediation of amphetamine-induced long-term depression of synaptic transmission by CB1 cannabinoid receptors in the rat amygdala. J Neurosci. 2003 Nov 12;23(32):10311-20. doi: 10.1523/JNEUROSCI.23-32-10311.2003. PMID: 14614090; PMCID: PMC6741012. ↥

  56. Haijen E, Farre M, de la Torre R, Pastor A, Olesti E, Pizarro N, Ramaekers JG, Kuypers KPC (2018): Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication. Psychopharmacology (Berl). 2018 Mar;235(3):709-717. doi: 10.1007/s00213-017-4787-2. PMID: 29143869; PMCID: PMC5847074. ↥

  57. Dlugos AM, Hamidovic A, Hodgkinson CA, Goldman D, Palmer AA, de Wit H (2010): More aroused, less fatigued: fatty acid amide hydrolase gene polymorphisms influence acute response to amphetamine. Neuropsychopharmacology. 2010 Feb;35(3):613-22. doi: 10.1038/npp.2009.166. PMID: 19890266; PMCID: PMC2945903. ↥

  58. Coelho AA, Lima-Bastos S, Gobira PH, Lisboa SF (2023): Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders. Neuronal Signal. 2023 Jul 25;7(2):NS20220034. doi: 10.1042/NS20220034. PMID: 37520658; PMCID: PMC10372471. REVIEW ↥

  59. Reyes-Cabello C, Alen F, Gómez R, Serrano A, Rivera P, Orio L, Rodríguez de Fonseca F, Pavón FJ (2012): Effects of the anandamide uptake blocker AM404 on food intake depend on feeding status and route of administration. Pharmacol Biochem Behav. 2012 Mar;101(1):1-7. doi: 10.1016/j.pbb.2011.11.011. PMID: 22133635. ↥

  60. Demaili A, Portugalov A, Dudai M, Maroun M, Akirav I, Braun K, Bock J (2023): Epigenetic (re)programming of gene expression changes of CB1R and FAAH in the medial prefrontal cortex in response to early life and adolescence stress exposure. Front Cell Neurosci. 2023 Feb 22;17:1129946. doi: 10.3389/fncel.2023.1129946. PMID: 36909279; PMCID: PMC9992175. ↥

  61. Patel S, Roelke CT, Rademacher DJ, Hillard CJ (2005): Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur J Neurosci. 2005 Feb;21(4):1057-69. doi: 10.1111/j.1460-9568.2005.03916.x. PMID: 15787710. ↥

  62. Kamprath K, Marsicano G, Tang J, Monory K, Bisogno T, Di Marzo V, Lutz B, Wotjak CT (2006): Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes. J Neurosci. 2006 Jun 21;26(25):6677-86. doi: 10.1523/JNEUROSCI.0153-06.2006. PMID: 16793875; PMCID: PMC6673838. ↥

  63. Fride E, Suris R, Weidenfeld J, Mechoulam R (2005): Differential response to acute and repeated stress in cannabinoid CB1 receptor knockout newborn and adult mice. Behav Pharmacol. 2005 Sep;16(5-6):431-40. doi: 10.1097/00008877-200509000-00016. PMID: 16148448. ↥

  64. Hill MN, McLaughlin RJ, Bingham B, Shrestha L, Lee TT, Gray JM, Hillard CJ, Gorzalka BB, Viau V (2010): Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9406-11. doi: 10.1073/pnas.0914661107. PMID: 20439721; PMCID: PMC2889099. ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥

  65. Gorzalka BB, Hill MN, Hillard CJ (2008): Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders. Neurosci Biobehav Rev. 2008 Aug;32(6):1152-60. doi: 10.1016/j.neubiorev.2008.03.004. PMID: 18433869. REVIEW ↥

  66. Steiner, Wotjak (2008): Role of the endocannabinoid system in regulation of the hypothalamic-pituitary-adrenocortical axis. Prog Brain Res. 2008;170:397-432. doi: 10.1016/S0079-6123(08)00433-0. ↥

  67. Cota D, Steiner MA, Marsicano G, Cervino C, Herman JP, Grübler Y, Stalla J, Pasquali R, Lutz B, Stalla GK, Pagotto U (2007): Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology. 2007 Apr;148(4):1574-81. doi: 10.1210/en.2005-1649. PMID: 17194743. ↥

  68. Patel S, Hillard CJ (2008): Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation. Eur J Neurosci. 2008 Jun;27(11):2821-9. doi: 10.1111/j.1460-9568.2008.06266.x. PMID: 18588527; PMCID: PMC2593941. REVIEW ↥

  69. Wolf, Calabrese (2020): Stressmedizin & Stresspsychologie; Seite 84 ↥

  70. Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ (2004): Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology. 2004 Dec;145(12):5431-8. doi: 10.1210/en.2004-0638. PMID: 15331569. ↥

  71. Morena M, Patel S, Bains JS, Hill MN (2016): Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology. 2016 Jan;41(1):80-102. doi: 10.1038/npp.2015.166. PMID: 26068727; PMCID: PMC4677118. REVIEW ↥ ↥

  72. Mizrahi R, Kenk M, Suridjan I, Boileau I, George TP, McKenzie K, Wilson AA, Houle S, Rusjan P (2014): Stress-induced dopamine response in subjects at clinical high risk for schizophrenia with and without concurrent cannabis use. Neuropsychopharmacology. 2014 May;39(6):1479-89. doi: 10.1038/npp.2013.347. PMID: 24385130; PMCID: PMC3988552. ↥ ↥ ↥

  73. Hill MN, Patel S, Carrier EJ, Rademacher DJ, Ormerod BK, Hillard CJ, Gorzalka BB (2005): Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology. 2005 Mar;30(3):508-15. doi: 10.1038/sj.npp.1300601. PMID: 15525997. ↥ ↥

  74. Lomazzo E, Bindila L, Remmers F, Lerner R, Schwitter C, Hoheisel U, Lutz B (2015): Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. Neuropsychopharmacology. 2015 Jan;40(2):488-501. doi: 10.1038/npp.2014.198. PMID: 25100669; PMCID: PMC4443964. ↥

  75. Bravo L, Mico JA, Rey-Brea R, Pérez-Nievas B, Leza JC, Berrocoso E (2012): Depressive-like states heighten the aversion to painful stimuli in a rat model of comorbid chronic pain and depression. Anesthesiology. 2012 Sep;117(3):613-25. doi: 10.1097/ALN.0b013e3182657b3e. PMID: 22846678. ↥

  76. Hill MN, Carrier EJ, McLaughlin RJ, Morrish AC, Meier SE, Hillard CJ, Gorzalka BB (2008): Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment. J Neurochem. 2008 Sep;106(6):2322-36. doi: 10.1111/j.1471-4159.2008.05567.x. PMID: 18643796; PMCID: PMC2606621. ↥ ↥

  77. Bai M, Zhu X, Zhang L, Zhang Y, Xue L, Wang Y, Zhong M, Zhang X (2017): Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study. Brain Behav. 2017 Sep 8;7(10):e00808. doi: 10.1002/brb3.808. PMID: 29075568; PMCID: PMC5651392. ↥

  78. Mlost J, Wąsik A, Starowicz K (2019): Role of endocannabinoid system in dopamine signalling within the reward circuits affected by chronic pain. Pharmacol Res. 2019 May;143:40-47. doi: 10.1016/j.phrs.2019.02.029. PMID: 30831242. REVIEW ↥

  79. Rademacher DJ, Meier SE, Shi L, Ho WS, Jarrahian A, Hillard CJ (2008): Effects of acute and repeated restraint stress on endocannabinoid content in the amygdala, ventral striatum, and medial prefrontal cortex in mice. Neuropharmacology. 2008 Jan;54(1):108-16. doi: 10.1016/j.neuropharm.2007.06.012. PMID: 17675104. ↥

  80. Hill MN, Kumar SA, Filipski SB, Iverson M, Stuhr KL, Keith JM, Cravatt BF, Hillard CJ, Chattarji S, McEwen BS (2013): Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. Mol Psychiatry. 2013 Oct;18(10):1125-35. doi: 10.1038/mp.2012.90. PMID: 22776900; PMCID: PMC4148304. ↥

  81. Hill MN, McLaughlin RJ, Morrish AC, Viau V, Floresco SB, Hillard CJ, Gorzalka BB (2009): Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology. 2009 Dec;34(13):2733-45. doi: 10.1038/npp.2009.114. PMID: 19710634; PMCID: PMC3197779. ↥ ↥

  82. Mizrahi R (2016): Social Stress and Psychosis Risk: Common Neurochemical Substrates? Neuropsychopharmacology. 2016 Feb;41(3):666-74. doi: 10.1038/npp.2015.274. PMID: 26346639; PMCID: PMC4707841. REVIEW ↥

  83. Littleton JM, Maclean KI, Brownlee G (1976): Proceedings: Alterations in dopamine uptake in rat corpus striatum induced by combinations of stress and delta8-tetrahydrocannabinol (delta8-THC). Br J Pharmacol. 1976 Mar;56(3):370P. PMID: 1260199; PMCID: PMC1666924. ↥

  84. MacLean KI, Littleton JM (1977): Environmental stress as a factor in the response of rat brain catecholamine metabolism to delta8-tetrahydrocannabinol. Eur J Pharmacol. 1977 Jan 21;41(2):171-82. doi: 10.1016/0014-2999(77)90206-0. PMID: 832673. ↥

  85. Suplita RL 2nd, Eisenstein SA, Neely MH, Moise AM, Hohmann AG (2008): Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia. Neuropharmacology. 2008 Jan;54(1):161-71. doi: 10.1016/j.neuropharm.2007.07.006. PMID: 17714742; PMCID: PMC2771679. ↥

  86. Schifani C, Pruessner J, Tseng HH, Rao N, Tagore A, Wilson AA, Houle S, Rusjan PM, Mizrahi R (2020): Stress-induced cortical dopamine response is altered in subjects at clinical high risk for psychosis using cannabis. Addict Biol. 2020 Jul;25(4):e12812. doi: 10.1111/adb.12812. PMID: 31389139. ↥

  87. Alteba S, Portugalov A, Hillard CJ, Akirav I (2021): Inhibition of Fatty Acid Amide Hydrolase (FAAH) During Adolescence and Exposure to Early Life Stress may Exacerbate Depression-like Behaviors in Male and Female Rats. Neuroscience. 2021 Feb 10;455:89-106. doi: 10.1016/j.neuroscience.2020.12.022. PMID: 33359656. ↥

  88. Portugalov A, Zaidan H, Gaisler-Salomon I, Hillard CJ, Akirav I (2022): FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats. Int J Mol Sci. 2022 Dec 17;23(24):16101. doi: 10.3390/ijms232416101. PMID: 36555739; PMCID: PMC9782513. ↥

  89. Alteba S, Korem N, Akirav I (2016): Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood. Learn Mem. 2016 Jun 17;23(7):349-58. doi: 10.1101/lm.041608.116. PMID: 27317195; PMCID: PMC4918780. ↥

  90. Alteba S, Mizrachi Zer-Aviv T, Tenenhaus A, Ben David G, Adelman J, Hillard CJ, Doron R, Akirav I (2020): Antidepressant-like effects of URB597 and JZL184 in male and female rats exposed to early life stress. Eur Neuropsychopharmacol. 2020 Oct;39:70-86. doi: 10.1016/j.euroneuro.2020.08.005. PMID: 32891517. ↥

  91. Portugalov A, Akirav I (2024): FAAH Inhibition Reverses Depressive-like Behavior and Sex-Specific Neuroinflammatory Alterations Induced by Early Life Stress. Cells. 2024 Nov 14;13(22):1881. doi: 10.3390/cells13221881. PMID: 39594629; PMCID: PMC11593135. ↥

  92. Dragon J, Gołyszny M, Zieliński M, Popiołek-Barczyk K, Starowicz K, Obuchowicz E (2025): Escitalopram reverses anxiety-like and despair behavior and affects endocannabinoid-related genes expression in the brain of adolescent male rats subjected to early life stress. Neuroscience. 2025 Jan 4;567:96-108. doi: 10.1016/j.neuroscience.2025.01.001. PMID: 39761822. ↥

  93. Di Bartolomeo M, Stark T, Di Martino S, Iannotti FA, Ruda-Kucerova J, Romano GL, Kuchar M, Laudani S, Palivec P, Piscitelli F, Wotjak CT, Bucolo C, Drago F, Di Marzo V, D’Addario C, Micale V (2023): The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology. Int J Mol Sci. 2023 Feb 15;24(4):3907. doi: 10.3390/ijms24043907. PMID: 36835313; PMCID: PMC9962163. ↥

  94. Stark T, Di Bartolomeo M, Di Marco R, Drazanova E, Platania CBM, Iannotti FA, Ruda-Kucerova J, D’Addario C, Kratka L, Pekarik V, Piscitelli F, Babinska Z, Fedotova J, Giurdanella G, Salomone S, Sulcova A, Bucolo C, Wotjak CT, Starcuk Z Jr, Drago F, Mechoulam R, Di Marzo V, Micale V (2020): Altered dopamine D3 receptor gene expression in MAM model of schizophrenia is reversed by peripubertal cannabidiol treatment. Biochem Pharmacol. 2020 Jul;177:114004. doi: 10.1016/j.bcp.2020.114004. PMID: 32360362. ↥

  95. Stark T, Ruda-Kucerova J, Iannotti FA, D’Addario C, Di Marco R, Pekarik V, Drazanova E, Piscitelli F, Bari M, Babinska Z, Giurdanella G, Di Bartolomeo M, Salomone S, Sulcova A, Maccarrone M, Wotjak CT, Starcuk Z Jr, Drago F, Mechoulam R, Di Marzo V, Micale V (2019): Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia. Neuropharmacology. 2019 Mar 1;146:212-221. doi: 10.1016/j.neuropharm.2018.11.035. PMID: 30496751. ↥ ↥

  96. Jongen-Rêlo AL, Leng A, Lüber M, Pothuizen HH, Weber L, Feldon J (2004): The prenatal methylazoxymethanol acetate treatment: a neurodevelopmental animal model for schizophrenia? Behav Brain Res. 2004 Mar 2;149(2):159-81. doi: 10.1016/s0166-4328(03)00228-6. PMID: 15129780. ↥