I must have misremembered. Looking at the anxiolytic study again, it appears s-limonene was used. I can find nothing on d-limonene in that regard.
Byron J Richards is very enthusiastic about D-Limonene (and sells a D-Limonene product).
Snippet from an article from Byron J Richard's Wellness Resources site:
http://www.wellnessr...ty_breast_canc/
Anxiety, Sleep & Mood
D-Limonene is a selective activator of the adenosine A(2A) receptor on cell membranes, which senses molecules outside the cell and in turn triggers activity within the cell. These receptors are vital for nervous system function. The lack of their activation is associated with anxiety, insomnia, and impaired dopamine transmission (addictive tendencies and lack of motivation). A lack of activation of adenosine A(2A) receptors on immune cells results in a hyperimmune response (allergic reactions).
Various doses of d-Limonene have a potent anti-anxiety effect. Even inhaling the vapors of d-Limonene can calm down nervesas well as allergic reactions.
Taking d-Limonene before bedtime will help calm nerves and promote restful sleep, yet another benefit of this multitalented nutrient.
I take a 500 mg capsule of limonene with my evening meal. Around 45 mins after the meal, I do typically feel a sense of relaxation (that feels cleaner somehow than e.g., the sleepiness you get from say eating a bunch of carbs). I'd vaguely wondered what might be causing it. But I take so many supplements with my evening meal - narrowing down what is causing the relaxation response would be a chore.
Some of the studies referenced in Byron J Richard's article - this all seems to be work with mice:
http://www.wellnessr...reduces_anxiety
D-Limonene Reduces Anxiety
Byron's Comments:
D-Limonene has a nerve relaxing effect.
Study Title:
Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action.
Study Abstract:
The aim of the study is to determine the acute toxicity and anxiolytic-like effects of a mixture of cis and trans of (+)-limonene epoxide in animal models of anxiety. After acute treatment with (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg (i.p.) no mortality was noted during 14 days of observation. In general, behavior, food and water consumption showed no significant changes. In open field test, (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg, after intraperitoneal administration, significantly decreased the number of crossings, grooming and rearing (p<0.001). All these effects were reversed by the pre-treatment with flumazenil (25 mg/kg, i.p.), similar to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, (+)-limonene epoxide increased the time of permanence and the number of entrances in the open arms. All these effects were reversed by flumazenil, an antagonist of benzodiazepine receptors. In addition, (+)-limonene epoxide (75 mg/kg) also produced a significant inhibition of the motor coordination (p<0.01), that was reversed by flumazenil. In conclusion, the present work evidenced sedative and anxiolytic-like effects of (+)-limonene epoxide, which might involve an action on benzodiazepine-type receptors. These results indicate that the properties of (+)-limonene epoxide should be more thoroughly examined in order to achieve newer tools for management and/or treatment of central nervous system diseases and anxiolytic-like effects. The LD50 obtained for the acute toxicity studies using intraperitoneal route of administration was 4.0 g/kg. These findings suggest that acute administration of the (+)-limonene epoxide exerts an anxiolytic-like effect on mice, and it could serve as a new approach for the treatment anxiety, since it practically does not produce toxic effects.
Study Information:
de Almeida AA, Costa JP, de Carvalho RB, de Sousa DP, de Freitas RM. Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res. 2012 April 11;1448:56-62.
Department of Chemistry of Federal University of Piauí, CEP 64.049-550, Teresina, Piauí, Brazil.
Anti-Anxiety Properties of D-Limonene
Byron's Comments:
Data showing the nerve relaxing effects of D-Limonene.
Study Title:
Anxiolytic-like activity and GC-MS analysis of ®-(+)-limonene fragrance, a natural compound found in foods and plants.
Study Abstract:
The traditional use of essential oils in aromatherapy has offered numerous health benefits. However, few scientific studies have been conducted with these oils to confirm their therapeutic efficacy. (+)-Limonene is a chemical constituent of various bioactive essential oils. The present study reports on the anxiolytic-like effects of (+)-limonene in an elevated maze model of anxiety in mice. At concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by inhalation, significantly modified all the parameters evaluated in the elevated plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not blocked by flumazenil. Analysis of (+)-limonene using gas chromatography-mass spectrometry (GC-MS) showed its volatility to be high. These data suggest possible connections between the volatility of (+)-limonene and its anxiolytic-like effect on the parameters evaluated in the elevated plus maze test. The data indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.
Study Information:
Lima NG, De Sousa DP, Pimenta FC, Alves MF, De Souza FS, Macedo RO, Cardoso RB, de Morais LC, Melo Diniz MD, de Almeida RN. Anxiolytic-like activity and GC-MS analysis of ®-(+)-limonene fragrance, a natural compound found in foods and plants. Pharmacol Biochem Behav. 2012 September
Departamento de Ciências Farmacêuticas da Universidade Federal da Paraíba, CEP 58051-970, João Pessoa, Paraíba, Brazil.
D-Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors.
Byron's Comments:
D-Limonene helps an important receptor work better, helping to calm nerves.
Study Title:
Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors.
Study Abstract:
Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors.
Study Information:
Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. 2011 January 7;404(1):345-8.
Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea.
As a bonus, you might get an anti-glycation effect:
Anti-glycation Activity of Limonene
Byron's Comments:
A novel mechanism of health protection.
Study Title:
A novel mechanism for antiglycative action of limonene through stabilization of protein conformation.
Study Abstract:
Inhibition of protein glycation is known to ameliorate secondary complications in diabetes. In the present study antiglycative properties of limonene, a natural product, were evaluated using BSA as a model protein. AMG (aminoguanidine) was used as a positive control. Measurement of total AGEs (Advanced Glycation End-products) and specific AGEs revealed that limonene could inhibit protein glycation to the extent of 56.3% and 75.1% respectively at 50 μM concentration as against 54.4% and 82.2% by AMG at 1 mM. Congo red binding and CD (Circular Dichroism) analysis revealed inhibition of α-helix to β-sheet transition wherein 18.5% β-sheet structures were observed in glycated BSA (bovine serum albumin) as against 4.9% with limonene. Glycation of protein in the presence of urea was enhanced by 18%, while in the presence of limonene it was reduced by 23% revealing the stabilizing effect of limonene. Electrophoretic mobility was similar to the normal control and a zeta potential value of -12.1 mV as against -15.1 mV in diabetic control was observed. Inhibition of glycation in limonene treated samples was confirmed through LC-MS analysis wherein AGEs such as pentosidine, CML (Nε-(carboxymethyl)lysine), CEL (Nε-(carboxyethyl)lysine), MOLD (methylglyoxal-lysine dimer) and imidazolone observed in glycated samples were absent in limonene treated samples. PatchDock studies revealed that limonene could bind to the major glycation sites IB, IIA and IIB sub domains and AMG to the IIIA sub domain. Thus limonene is a potent protein glycation inhibitor that prevents protein glycation through a novel mechanism of stabilization of protein structure through hydrophobic interactions.
Study Information:
Joglekar MM, Panaskar SN, Chougale AD, Kulkarni MJ, Arvindekar AU. A novel mechanism for antiglycative action of limonene through stabilization of protein conformation. Mol Biosyst 2013 July
Department of Biochemistry, Shivaji University, Kolhapur, 416004, Maharashtra, India.
Edited by blood, 29 September 2013 - 07:47 AM.