The DOI matches its Crossref record; 89 of the 89 references it cites were found in a registry or an index.
More surprises lying ahead. The endocannabinoids keep us guessing
Open accessAbstract
The objective of this review is to point out some important facts that we don't know about endogenous cannabinoids - lipid-derived signaling molecules that activate CB1 cannabinoid receptors and play key roles in motivation, emotion and energy balance. The first endocannabinoid substance to be discovered, anandamide, was isolated from brain tissue in 1992. Research has shown that this molecule is a bona fide brain neurotransmitter involved in the regulation of stress responses and pain, but the molecular mechanisms that govern its formation and the neural pathways in which it is employed are still unknown. There is a general consensus that enzyme-mediated cleavage, catalyzed by fatty acid amide hydrolase (FAAH), terminates the biological actions of anandamide, but there are many reasons to believe that other as-yet-unidentified proteins are also involved in this process. We have made significant headway in understanding the second arrived in the endocannabinoid family, 2-arachidonoyl-sn-glycerol (2-AG), which was discovered three years after anandamide. Researchers have established some of the key molecular players involved in 2-AG formation and deactivation, localized them to specific synaptic components, and showed that their assembly into a multi-molecular protein complex (termed the '2-AG signalosome') allows 2-AG to act as a retrograde messenger at excitatory synapses of the brain. Basic questions that remain to be answered pertain to the exact molecular composition of the 2-AG signalosome, its regulation by neural activity and its potential role in the actions of drugs of abuse such as Δ(9)-THC and cocaine. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Fatty acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the endocannabinoid anandamide.”
From Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment (2016) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990) · Nature · doi:10.1038/346561a0 · Cited by 5,011
Identification of two related pentapeptides from the brain with potent opiate agonist activity
Hughes, J., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., & Morris, H. R. (1975) · Nature · doi:10.1038/258577a0 · Cited by 3,806
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00109-d · Cited by 2,913
Determination and characterization of a cannabinoid receptor in rat brain
Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S., & Howlett, A. C. (1988) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09876-1 · Cited by 2,443 · cited 2×
“…the molecular characterization of a cell-surface receptor that recognizes marijuana’s main psychoactive constituent, Δ9-tetrahydrocannabinol (Δ9-THC)(Devane et al., 1988; Matsuda et al., 1990), had finally answered the longstanding question of how this compound exerts its unique brand of…”
Opiate Receptor: Demonstration in Nervous Tissue
Pert, C. B., & Snyder, S. H. (1973) · Science · doi:10.1126/science.179.4077.1011 · Cited by 2,389
2-Arachidonoylgylcerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2437 · Cited by 2,196
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
Formation and inactivation of endogenous cannabinoid anandamide in central neurons
Marzo, V. D., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D. (1994) · Nature · doi:10.1038/372686a0 · Cited by 1,585
Self-citationA second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496
Self-citation
Cited by
Sorted by citations
Items 101–127 of 127
Distinct endocannabinoids specifically signal to astrocytes and neuronsPreprint
Noriega‐Prieto, J. A., Falcón‐Moya, R., Eraso‐Pichot, A., Fundazuri, U. B., Guttipatti, P., Belisle, L., Moreno, A. R., van der Stelt, M., Cheer, J. F., Marsicano, G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.13.544877 · Cited by 3
Cannabinoids in Autism and Fragile X Syndrome: Value-Based Treatment Revolution Ahead?
Pavlovic, Z. M. (2017) · Global Journal of Intellectual & Developmental Disabilities · doi:10.19080/gjidd.2017.03.555601 · Cited by 1
Richter, A., Sason, A., Adelson, M., Frish, O., & Peles, E. (2020) · Journal of Addictive Diseases · doi:10.1080/10550887.2020.1773730 · Cited by 2
Bagüés, A., & Goicoechea, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800213-1.00065-1 · Cited by 2
Kroll, S. L., Hulka, L. M., Kexel, A.-K., Vonmoos, M., Preller, K. H., Treyer, V., Ametamey, S. M., Baumgartner, M. R., Boost, C., Pahlisch, F., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.18.537293 · Cited by 2
Bazán, H. A., Bhattacharjee, S., Reid, M. M., Jun, B., Polk, C., Strain, M., Pierre, L. S., Desai, N. N., Daly, P. L., Cucinello‐Ragland, J. A., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2883310/v1 · Cited by 2
Sponsor's foreword: NIDA at forty
Shurtleff, D., Sasek, C. A., & Kautz, M. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.08.020 · Cited by 1
Cannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2022) · Springer eBooks · doi:10.1007/978-1-4614-6434-1_136-2 · Cited by 1
Self-citationOxygenation of Anandamide by Lipoxygenases
van Zadelhoff, G., & van der Stelt, M. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2728-0_26 · Cited by 1
Therapeutic application of cannabis and its derivatives
Chattopadhyay, M., Chanda, A., & Bhattacharya, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15489-8.00003-7 · Cited by 1
Piomelli, D. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.01.010 · Cited by 1
Self-citationCannabinoids and Endocannabinoids
Jung, K., & Piomelli, D. (2022) · Springer eBooks · doi:10.1007/978-3-030-88832-9_136 · Cited by 1
Self-citationEndocannabinoid signaling at excitatory and inhibitory synapses
Liang, J., & Wierenga, C. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90877-1.00022-x · Cited by 1
Exciting inhibition: Local regulation of synapse formation and plasticity
Kruijssen, D. L. H. (2020) · Utrecht University Repository (Utrecht University) · doi:10.33540/296
Ahmed, M. (2020) · TSpace (University of Toronto)
de Almeida, C. M. O. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2021.tde-05072021-154535
Liang, J. (2022) · Utrecht University Repository (Utrecht University) · doi:10.33540/1112
Cannabinoide zur Schmerzbehandlung
Mosley, C. I., Gaynor, J. S., Cital, S. N., & Brassard, J. (2024) · Springer eBooks · doi:10.1007/978-3-031-67821-9_5
Adolescence as a Window of Vulnerability to Cannabis Use: Insights from Animal Studies
Jung, K., Lee, H.-L., & Piomelli, D. (2025) · Springer eBooks · doi:10.1007/978-3-031-87990-6_11
Self-citationPotential mechanisms of endocannabinoid release
Lupica, C. R. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00006-2
Rodriguez, A. G. (2016) · theses.fr (ABES) · doi:10.70675/ecd0f3cbz19d7z406bza88eze6d1c4e9be0e
Role of the type-1 cannabinoid receptor in the control of water intake
Zhao, Z. (2019) · theses.fr (ABES) · doi:10.70675/ca103186z8d92z4d94zaf67zcce657f39cd1
Roles of astroglial cannabinoid type 1 receptors (CB1) in memory and synaptic plasticity
Robin, L. M. (2018) · theses.fr (ABES) · doi:10.70675/1fd1dda8z3f4bz404azbdf6z5b648e4c4053
Salviati, S., Braccagni, G., Corridori, E., Sabatini, G., Fanti, F., Guzzi, F., M, P., Battista, N., Scheggi, S., & Gambarana, C. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.110996
Development and Preclinical Safety Evaluation of an Injectable β-Caryophyllene Nanoemulsion
Viana, A. B. S., Lobato-Santos, N. G., Alberto, A. K. M., dos Santos, A. V. T. D. L. T., Brito, S. G. L., Colares, N. N. D., & Carvalho, J. C. T. (2026) · Pharmaceuticals · doi:10.3390/ph19050763
The how and why for multiple forms of hippocampal LTP
Gall, C. M., Le, A. A., & LYNCH, G. S. (2026) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2026.1855059
Metadata
- Authors
- Piomelli, D.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Piomelli, Daniele
- ORCID
- Piomelli, Daniele
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 76
- Pages
- 228-234
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3855347
- OpenAlex
- W2030135878
- Cited by
- 128
- References
- 89
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 13 · 2021: 11 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 13 · 2016: 17 · 2015: 20 · 2014: 17
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Drug Abuse (DA012413, R01DA012413, DA-031387, DP1DA031387)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- endocannabinoids, anandamide, fatty acid amide hydrolase, retrograde signaling, CB1 receptor, stress response, pain, drug abuse, delta-9-tetrahydrocannabinol, cocaine
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Humans, Substance-Related Disorders, Receptors, Cannabinoid, Polyunsaturated Alkamides, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
